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REVIEW
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Conventional and functionalised nanostructured lipid carriers for pulmonary-targeted delivery systems

Maxius Gunawan1 ,  Kurnia Sari Setio Putri2 ,  Annalisa Tirella3,4 ,  Jittima Amie Luckanagul1,5 ,  David G. Fernig6 ,  Veerakiet Boonkanokwong1*
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1 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
2 Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, West Java, Indonesia
3 BIOtech Center for Biomedical Technologies, Department of Industrial Engineering, University of Trento, Via delle Regole, Trento, Italy
4 Division of Pharmacy and Optometry, School of Health Science, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
5 Center of Excellence in Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand
6 Department of Biochemistry, Systems and Cell Biology, Institute of Systems, Molecular and Integrated Biology, University of Liverpool, Liverpool, United Kingdom
BMT, 00055 https://doi.org/10.12336/bmt.25.00055
Submitted: 1 June 2025 | Revised: 17 August 2025 | Accepted: 18 August 2025 | Published: 2 October 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Pulmonary delivery systems are potential routes for numerous lung-related disease treatments. The pulmonary delivery system can be utilised for local deposition and systemic application due to its large surface area and high vascularisation within the alveolar epithelium. This can lead to high permeability and bioavailability of drugs. This review explores the utilisation of conventional nanostructured lipid carriers in pulmonary delivery system applications. Due to their high entrapment efficiency, stability, and biocompatibility, nanostructured lipid carriers can be used as drug carriers through the pulmonary delivery system. Using nanostructured lipid carriers can enhance drug deposition into deeper lungs, improve bioavailability and efficacy, provide sustained and controlled release profiles of drugs, enhance antimicrobial activity, enhance cellular uptake and penetration, and improve bioavailability. However, conventional nanostructured lipid carriers have a major drawback: low selectivity in target cells. The non-selective properties of these carriers can lead to potential side effects, high toxicity, and reduced effectiveness. Therefore, recent applications of functionalised nanostructured lipid carriers have been evaluated through in vitro and in vivo studies to prove their safety and effectiveness in pulmonary-targeted delivery. Nanostructured lipid carriers have been functionalised to improve their selectivity and effectiveness. This review discusses various functionalised nanostructured lipid carriers through surface modification and their mechanism, including hydrophilic polymers, polysaccharides, peptides and proteins, small molecules, surfactants, genes, antibodies, and pH-sensitive polymers. Furthermore, key case studies in clinical translation are examined to illustrate the practical applications and progress of these advanced nanocarriers. This review also discusses the potential challenges in development, including pulmonary-specific targeting, toxicity, and immunogenicity concerns, as well as production and scalability challenges. Moreover, developing functionalised nanocarriers presents new opportunities by highlighting effective strategies to address existing challenges and accelerate their progression from experimental research to clinical translation.

Keywords
Nanostructured lipid carriers
Pulmonary-targeted delivery system
Lipid nanoparticles
Functionalisation
Surface modification
Active targeting
Funding
This research project was supported by the Faculty of Pharmaceutical Sciences Fund, Chulalongkorn University (Grant number Phar2567_RG010). The authors expressed their gratitude to the Research and Innovation Affairs, Faculty of Pharmaceutical Sciences, Chulalongkorn University, for providing a research fund to V.B. BioRender software, and the licensing rights of all figures published in this article were supported by this research fund. M.G. was supported by the ASEAN or Non-ASEAN Countries Scholarship (Award Number: 2022-2-18), Office of Academic Affairs, Chulalongkorn University.
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References

Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.

  1. Patil JS, Sarasija S. Pulmonary drug delivery strategies: A concise, systematic review. Lung India. 2012;29(1):44-49. doi: 10.4103/0970-2113.92361

 

  1. He S, Gui J, Xiong K, Chen M, Gao H, Fu Y. A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases. J Nanobiotechnol. 2022;20(1):101. doi: 10.1186/s12951-022-01307-x

 

  1. Ibrahim M, Verma R, Garcia-Contreras L. Inhalation drug delivery devices: Technology update. Med Devices (Auckl). 2015;8:131-139. doi: 10.2147/mder.S48888

 

  1. Wang B, Wang L, Yang Q, et al. Pulmonary inhalation for disease treatment: Basic research and clinical translations. Mater Today Bio. 2024;25:100966. doi: 10.1016/j.mtbio.2024.100966

 

  1. Hastedt JE, Bäckman P, Cabal A, et al. iBCS: 3. A biopharmaceutics classification system for orally inhaled drug products. Mol Pharm. 2024;21(1):164-172. doi: 10.1021/acs.molpharmaceut.3c00685

 

  1. Ngan CL, Asmawi AA. Lipid-based pulmonary delivery system: A review and future considerations of formulation strategies and limitations. Drug Deliv Transl Res. 2018;8(5):1527-1544. doi: 10.1007/s13346-018-0550-4

 

  1. Javed S, Mangla B, Almoshari Y, Sultan MH, Ahsan W. Nanostructured lipid carrier system: A compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery. Nanotechnol Rev. 2022;11(1):1744-1777. doi: 10.1515/ntrev-2022-0109

 

  1. Elmowafy M, Al-Sanea MM. Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies. Saudi Pharm J. 2021;29(9):999-1012. doi: 10.1016/j.jsps.2021.07.015

 

  1. Gunawan M, Fernig DG, Boonkanokwong V. Screening and characterization of favipiravir-loaded nanostructured lipid carrier formulations by using A 26-2 fractional factorial design. Int J Appl Pharm. 2025;17(4):254-267 doi: 10.22159/ijap.2025v17i4.53891

 

  1. Wilie YBA, Gunawan M, Hadad Y, et al. Revolutionizing colon-targeted drug delivery: The pivotal role of lipid nano-carriers and their transformative modifications. J Drug Deliv Sci Technol. 2025;113:107319. doi: 10.1016/j.jddst.2025.107319

 

  1. Fang CL, Al-Suwayeh SA, Fang JY. Nanostructured lipid carriers (NLCs) for drug delivery and targeting. Recent Pat Nanotechnol. 2013;7(1):41-55.

 

  1. Selvamuthukumar S, Velmurugan R. Nanostructured lipid carriers: A potential drug carrier for cancer chemotherapy. Lipids Health Dis. 2012;11(1):159. doi: 10.1186/1476-511X-11-159

 

  1. Patil TS, Deshpande AS. Nanostructured lipid carriers-based drug delivery for treating various lung diseases: A state-of-the-art review. Int J Pharm. 2018;547(1-2):209-225. doi: 10.1016/j.ijpharm.2018.05.070

 

  1. Priya S, Desai VM, Singhvi G. Surface modification of lipid-based nanocarriers: A potential approach to enhance targeted drug delivery. ACS Omega. 2023;8(1):74-86. doi: 10.1021/acsomega.2c05976

 

  1. Rizwanullah M, Ahmad MZ, Garg A, Ahmad J. Advancement in design of nanostructured lipid carriers for cancer targeting and theranostic application. Biochim Biophys Acta Gen Subj. 2021;1865(9):129936. doi: 10.1016/j.bbagen.2021.129936

 

  1. Aung HH, Sivakumar A, Gholami SK, Venkateswaran SP, Gorain B, Shadab Md. Chapter 1 - An overview of the anatomy and physiology of the lung. In: Kesharwani P, editor. Nanotechnology-Based Targeted Drug Delivery Systems for Lung Cancer. United States: Academic Press; 2019. p. 1-20.

 

  1. Ruge CA, Kirch J, Lehr CM. Pulmonary drug delivery: From generating aerosols to overcoming biological barriers-therapeutic possibilities and technological challenges. Lancet Respir Med. 2013;1(5):402-413. doi: 10.1016/s2213-2600(13)70072-9

 

  1. Patel B, Gupta N, Ahsan F. Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome. Eur J Pharm Biopharm. 2015;89:163-174. doi: 10.1016/j.ejpb.2014.12.001

 

  1. Scheuch G, Kohlhaeufl MJ, Brand P, Siekmeier R. Clinical perspectives on pulmonary systemic and macromolecular delivery. Adv Drug Deliv Rev. 2006;58(9-10):996-1008. doi: 10.1016/j.addr.2006.07.009

 

  1. Nanjwade BK, Adichwal SA, Gaikwad KR, Parikh KA, Manvi FV. Pulmonary drug delivery: Novel pharmaceutical technologies breathe new life into the lungs. PDA J Pharm Sci Technol. 2011;65(5):513-534. doi: 10.5731/pdajpst.2011.00704

 

  1. Mishra B, Singh J. Novel drug delivery systems and significance in respiratory diseases. In: Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems. Netherlands: Elsevier; 2020. p. 18.

 

  1. Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl Lung Cancer Res. 2015;4(1):36-54. doi: 10.3978/j.issn.2218-6751.2014.05.01

 

  1. Mitchell JP, Nagel MW, Wiersema KJ, Doyle CC. Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: Comparison of Andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 Aerodynamic Particle Sizer aerosol spectrometer. AAPS PharmSciTech. 2003;4(4):E54. doi: 10.1208/pt040454

 

  1. Mekonnen T, Cai X, Burchell C, Gholizadeh H, Cheng S. A review of upper airway physiology relevant to the delivery and deposition of inhalation aerosols. Adv Drug Deliv Rev. 2022;191:114530. doi: 10.1016/j.addr.2022.114530

 

  1. Sanchis J, Corrigan C, Levy ML, Viejo JL. Inhaler devices - From theory to practice. Respir Med. 2013;107(4):495-502. doi: 10.1016/j.rmed.2012.12.007

 

  1. Nimmano N, Somavarapu S, Taylor KMG. Aerosol characterisation of nebulised liposomes co-loaded with erlotinib and genistein using an abbreviated cascade impactor method. Int J Pharm. 2018;542(1):8-17. doi: 10.1016/j.ijpharm.2018.02.035

 

  1. Liu J, Wu Z, Liu Y, et al. ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling. J Nanobiotechnol. 2022;20(1):213. doi: 10.1186/s12951-022-01435-4

 

  1. Elbardisy B, Boraie N, Galal S. Tadalafil nanoemulsion mists for treatment of pediatric pulmonary hypertension via nebulization. Pharmaceutics. 2022;14(12):2717. doi: 10.3390/pharmaceutics14122717

 

  1. Asmawi AA, Salim N, Abdulmalek E, Abdul Rahman MB. Size-controlled preparation of docetaxel- and curcumin-loaded nanoemulsions for potential pulmonary delivery. Pharmaceutics. 2023;15(2):652. doi: 10.3390/pharmaceutics15020652

 

  1. Craparo EF, Cabibbo M, Scialabba C, Giammona G, Cavallaro G. Inhalable formulation based on lipid-polymer hybrid nanoparticles for the macrophage targeted delivery of roflumilast. Biomacromolecules. 2022;23(8):3439-3451. doi: 10.1021/acs.biomac.2c00576

 

  1. Wadhwa A, Bobak TR, Bohrmann L, et al. Pulmonary delivery of siRNA-loaded lipid-polymer hybrid nanoparticles: Effect of nanoparticle size. OpenNano. 2023;13:100180. doi: 10.1016/j.onano.2023.100180

 

  1. Wang JL, Hanafy MS, Xu H, et al. Aerosolizable siRNA-encapsulated solid lipid nanoparticles prepared by thin-film freeze-drying for potential pulmonary delivery. Int J Pharm. 2021;596:120215. doi: 10.1016/j.ijpharm.2021.120215

 

  1. Esmaeili M, Aghajani M, Abbasalipourkabir R, Amani A. Budesonide-loaded solid lipid nanoparticles for pulmonary delivery: Preparation, optimization, and aerodynamic behavior. Artif Cells Nanomed Biotechnol. 2016;44(8):1964-1971. doi: 10.3109/21691401.2015.1129614

 

  1. Ahalwat S, Bhatt DC, Rohilla S, et al. Mannose-functionalized isoniazid-loaded nanostructured lipid carriers for pulmonary delivery: In vitro prospects and in vivo therapeutic efficacy assessment. Pharmaceuticals (Basel). 2023;16(8):1108. doi: 10.3390/ph16081108

 

  1. Gunawan M, Bestari AN, Ramadon D, Efendi A, Boonkanokwong V. Combination of lipid-based nanoparticles with microneedles as a promising strategy for enhanced transdermal delivery systems: A comprehensive review. J Drug Deliv Sci Technol. 2025;107:106807. doi: 10.1016/j.jddst.2025.106807

 

  1. Gunawan M, Boonkanokwong V. Current applications of solid lipid nanoparticles and nanostructured lipid carriers as vehicles in oral delivery systems for antioxidant nutraceuticals: A review. Colloids Surf B Biointerfaces. 2024;233:113608. doi: 10.1016/j.colsurfb.2023.113608

 

  1. Viegas C, Patrício AB, Prata JM, Nadhman A, Chintamaneni PK, Fonte P. Solid lipid nanoparticles vs. nanostructured lipid carriers: A comparative review. Pharmaceutics. 2023;15(6):1593. doi: 10.3390/pharmaceutics15061593

 

  1. Ahmad J, Amin S, Rahman M, et al. Solid matrix based lipidic nanoparticles in oral cancer chemotherapy: Applications and pharmacokinetics. Curr Drug Metab. 2015;16(8):633-644. doi: 10.2174/1389200216666150812122128

 

  1. Abdi Syahputra R, Dalimunthe A, Utari ZD, et al. Nanotechnology and flavonoids: Current research and future perspectives on cardiovascular health. J Funct Foods. 2024;120:106355. doi: 10.1016/j.jff.2024.106355

 

  1. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev. 2013;65(1):71-79. doi: 10.1016/j.addr.2012.10.002

 

  1. Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135-146. doi: 10.1016/j.jconrel.2010.08.027

 

  1. Ahmad J, Akhter S, Rizwanullah M, et al. Nanotechnology-based inhalation treatments for lung cancer: State of the art. Nanotechnol Sci Appl. 2015;8:55-66. doi: 10.2147/nsa.S49052

 

  1. Tewabe A, Abate A, Tamrie M, Seyfu A, Abdela Siraj E. Targeted drug delivery - from magic bullet to nanomedicine: Principles, challenges, and future perspectives. J Multidiscip Healthc. 2021;14:1711-1724. doi: 10.2147/jmdh.S313968

 

  1. Jyoti K, Kaur K, Pandey RS, Jain UK, Chandra R, Madan J. Inhalable nanostructured lipid particles of 9-bromo-noscapine, a tubulin-binding cytotoxic agent: In vitro and in vivo studies. J Colloid Interface Sci. 2015;445:219-230. doi: 10.1016/j.jcis.2014.12.092

 

  1. Liu H, Liu S, Ma P, et al. Development and evaluation of aloperine-loaded nanostructured lipid carriers for the treatment of pulmonary arterial hypertension. Int J Nanomed. 2025;20:871-886. doi: 10.2147/IJN.S489133

 

  1. Khan I, Hussein S, Houacine C, et al. Fabrication, characterization and optimization of nanostructured lipid carrier formulations using Beclomethasone dipropionate for pulmonary drug delivery via medical nebulizers. Int J Pharm. 2021;598:120376. doi: 10.1016/j.ijpharm.2021.120376

 

  1. Jaafar-Maalej C, Andrieu V, Elaissari A, Fessi H. Beclomethasone-loaded lipidic nanocarriers for pulmonary drug delivery: Preparation, characterization and in vitro drug release. J Nanosci Nanotechnol. 2011;113:1841-1851. doi: 10.1166/jnn.2011.3119

 

  1. Patlolla RR, Chougule M, Patel AR, Jackson T, Tata PNV, Singh M. Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers. J Control Release. 2010;144(2):233-241. doi: 10.1016/j.jconrel.2010.02.006

 

  1. Patel AR, Chougule MB, Townley I, Patlolla R, Wang G, Singh M. Efficacy of aerosolized celecoxib encapsulated nanostructured lipid carrier in non-small cell lung cancer in combination with docetaxel. Pharm Res. 2013;30(5):1435-1446. doi: 10.1007/s11095-013-0984-9

 

  1. Almurshedi AS, Aljunaidel HA, Alquadeib B, et al. Development of inhalable nanostructured lipid carriers for ciprofloxacin for noncystic fibrosis bronchiectasis treatment. Int J Nanomedicine. 2021;16:2405-2417. doi: 10.2147/ijn.S286896

 

  1. Sans-Serramitjana E, Fusté E, Martínez-Garriga B, et al. Killing effect of nanoencapsulated colistin sulfate on Pseudomonas aeruginosa from cystic fibrosis patients. J Cyst Fibros. 2016;15(5):611-618. doi: 10.1016/j.jcf.2015.12.005

 

  1. Sato MR, Oshiro Junior JA, Machado RT, et al. Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis. Drug Des Devel Ther. 2017;11:909-921. doi: 10.2147/dddt.S127048

 

  1. Kardara M, Hatziantoniou S, Sfika A, et al. Caveolar uptake and endothelial-protective effects of nanostructured lipid carriers in acid aspiration murine acute lung injury. Pharm Res. 2013;30(7):1836-1847. doi: 10.1007/s11095-013-1027-2

 

  1. Rawal S, Patel B, Patel MM. Fabrication, optimisation and in vitro evaluation of docetaxel and curcumin Co-loaded nanostructured lipid carriers for improved antitumor activity against non-small cell lung carcinoma. J Microencapsul. 2020;37(8):543-556. doi: 10.1080/02652048.2020.1823498

 

  1. Sherif AY, Harisa GI, Shahba AA, Alanazi FK, Qamar W. Optimization of gefitinib-loaded nanostructured lipid carrier as a biomedical tool in the treatment of metastatic lung cancer. Molecules. 2023;28(1). doi: 10.3390/molecules28010448

 

  1. Pardeike J, Weber S, Haber T, et al. Development of an Itraconazole-loaded nanostructured lipid carrier (NLC) formulation for pulmonary application. Int J Pharm. 2011;419(1):329-338. doi: 10.1016/j.ijpharm.2011.07.040

 

  1. Pardeike J, Weber S, Zarfl HP, Pagitz M, Zimmer A. Itraconazole-loaded nanostructured lipid carriers (NLC) for pulmonary treatment of aspergillosis in falcons. Eur J Pharm Biopharm. 2016;108:269-276. doi: 10.1016/j.ejpb.2016.07.018

 

  1. Patil-Gadhe A, Kyadarkunte A, Patole M, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro–in vivo aerosol performance. Eur J Pharm Biopharm. 2014;88(1):169-177. doi: 10.1016/j.ejpb.2014.07.007

 

  1. Huguet-Casquero A, Moreno-Sastre M, López-Méndez TB, Gainza E, Pedraz JL. Encapsulation of oleuropein in nanostructured lipid carriers: Biocompatibility and antioxidant efficacy in lung epithelial cells. Pharmaceutics. 2020;12(5):429. doi: 10.3390/pharmaceutics12050429

 

  1. Kaur P, Garg T, Rath G, Murthy RSR, Goyal AK. Development, optimization and evaluation of surfactant-based pulmonary nanolipid carrier system of paclitaxel for the management of drug resistance lung cancer using Box-Behnken design. Drug Deliv. 2016;23(6):1912-1925. doi: 10.3109/10717544.2014.993486

 

  1. Wang Y, Zhang H, Hao J, Li B, Li M, Xiuwen W. Lung cancer combination therapy: Co-delivery of paclitaxel and doxorubicin by nanostructured lipid carriers for synergistic effect. Drug Deliv. 2016;23(4):1398-1403. doi: 10.3109/10717544.2015.1055619

 

  1. Kaur P, Mishra V, Shunmugaperumal T, Goyal AK, Ghosh G, Rath G. Inhalable spray dried lipidnanoparticles for the co-delivery of paclitaxel and doxorubicin in lung cancer. J Drug Deliv Sci Technol. 2020;56:101502. doi: 10.1016/j.jddst.2020.101502

 

  1. Al Khatib AO, Yousfan A, Abed A, El-Tanani M, Al-Obaidi H. Development of pimozide spray dried lipid nanoparticles with enhanced targeting of non-small cell lung cancer. J Drug Deliv Sci Technol. 2025;109:106969. doi: 10.1016/j.jddst.2025.106969

 

  1. Chettupalli AK, Kakkerla A, Jadi RK, et al. Design, development, and preclinical evaluation of pirfenidone-loaded nanostructured lipid carriers for pulmonary delivery. Sci Rep. 2025;15(1):11390. doi: 10.1038/s41598-025-90910-7

 

  1. Patil-Gadhe A, Pokharkar V. Pulmonary targeting potential of rosuvastatin loaded nanostructured lipid carrier: Optimization by factorial design. Int J Pharm. 2016;501(1):199-210. doi: 10.1016/j.ijpharm.2016.01.080

 

  1. Pastor M, Moreno-Sastre M, Esquisabel A, et al. Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm. 2014;477(1):485-494. doi: 10.1016/j.ijpharm.2014.10.048

 

  1. Moreno-Sastre M, Pastor M, Esquisabel A, et al. Stability study of sodium colistimethate-loaded lipid nanoparticles. J Microencapsul. 2016;33(7):636-645. doi: 10.1080/02652048.2016.1242665

 

  1. Pastor M, Basas J, Vairo C, et al. Safety and effectiveness of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) against P. aeruginosa: In vitro and in vivo studies following pulmonary and intramuscular administration. Nanomedicine. 2019;18:101-111. doi: 10.1016/j.nano.2019.02.014

 

  1. Moreno-Sastre M, Pastor M, Esquisabel A, et al. Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis. Int J Pharm. 2016;498(1):263-273. doi: 10.1016/j.ijpharm.2015.12.028

 

  1. Khan I, Sabu M, Hussein N, et al. Trans-resveratrol-loaded nanostructured lipid carrier formulations for pulmonary drug delivery using medical nebulizers. J Pharm Sci. 2025;114(5):103713. doi: 10.1016/j.xphs.2025.103713

 

  1. Khan I, Sunita S, Hussein NR, et al. Development and characterization of novel combinations and compositions of nanostructured lipid carrier formulations loaded with trans-resveratrol for pulmonary drug delivery. Pharmaceutics. 2024;16(12):1589. doi: 10.3390/pharmaceutics16121589

 

  1. El-Sherbiny IM, El-Baz NM, Yacoub MH. Inhaled nano- and microparticles for drug delivery. Glob Cardiol Sci Pract. 2015;2015:2. doi: 10.5339/gcsp.2015.2

 

  1. Edwards DA, Ben-Jebria A, Langer R. Recent advances in pulmonary drug delivery using large, porous inhaled particles. J Appl Physiol (1985). 1998;85(2):379-385. doi: 10.1152/jappl.1998.85.2.379

 

  1. Boc S, Momin MAM, Farkas DR, Longest W, Hindle M. Performance of low air volume dry powder inhalers (LV-DPI) when aerosolizing excipient enhanced growth (EEG) surfactant powder formulations. AAPS PharmSciTech. 2021;22(4):135. doi: 10.1208/s12249-021-01998-9

 

  1. Mall J, Naseem N, Haider MF, Rahman MA, Khan S, Siddiqui SN. Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications. Intell Pharm. 2025;3(4):243-255. doi: 10.1016/j.ipha.2024.09.005

 

  1. Kumar M, Hilles AR, Almurisi SH, Bhatia A, Mahmood S. Micro and nano-carriers-based pulmonary drug delivery system: Their current updates, challenges, and limitations – A review. JCIS Open. 2023;12:100095. doi: 10.1016/j.jciso.2023.100095

 

  1. Kumar M, Virmani T, Kumar G, et al. Nanocarriers in tuberculosis treatment: Challenges and delivery strategies. Pharmaceuticals (Basel). 2023;16(10):1360. doi: 10.3390/ph16101360

 

  1. Murugan K, Choonara YE, Kumar P, Bijukumar D, du Toit LC, Pillay V. Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures. Int J Nanomedicine. 2015;10:2191-206. doi: 10.2147/ijn.S75615

 

  1. Eker F, Duman H, Akdaşçi E, et al. A comprehensive review of nanoparticles: From classification to application and toxicity. Molecules. 2024;29(15):3482. doi: 10.3390/molecules29153482

 

  1. Janssens HM, de Jongste JC, Hop WCJ, Tiddens HAWM. Extra-fine particles improve lung delivery of inhaled steroids in infantsa: A study in an upper airway model. Chest. 2003;123(6):2083-2088. doi: 10.1378/chest.123.6.2083

 

  1. Benke E, Winter C, Szabó-Révész P, Roblegg E, Ambrus R. The effect of ethanol on the habit and in vitro aerodynamic results of dry powder inhalation formulations containing ciprofloxacin hydrochloride. Asian J Pharm Sci. 2021;16(4):471-482. doi: 10.1016/j.ajps.2021.04.003

 

  1. Karimi K, Pallagi E, Szabó-Révész P, Csóka I, Ambrus R. Development of a microparticle-based dry powder inhalation formulation of ciprofloxacin hydrochloride applying the quality by design approach. Drug Des Devel Ther. 2016;10:3331-3343. doi: 10.2147/dddt.S116443

 

  1. Rawal T, Kremer L, Halloum I, Butani S. Dry-powder inhaler formulation of rifampicin: An improved targeted delivery system for alveolar tuberculosis. J Aerosol Med Pulm Drug Deliv. 2017;30(6):388-398. doi: 10.1089/jamp.2017.1379

 

  1. Vieira AC, Magalhães J, Rocha S, et al. Targeted macrophages delivery of rifampicin-loaded lipid nanoparticles to improve tuberculosis treatment. Nanomedicine (Lond). 2017;12(24):2721-2736. doi: 10.2217/nnm-2017-0248

 

  1. Shen Z, Fisher A, Liu WK, Li Y. 1 - PEGylated “stealth” nanoparticles and liposomes. In: Parambath A, editor. Engineering of Biomaterials for Drug Delivery Systems. New Delhi: Woodhead Publishing; 2018. p. 1-26.

 

  1. Gupta V, Bhavanasi S, Quadir M, et al. Protein PEGylation for cancer therapy: Bench to bedside. J Cell Commun Signal. 2019;13(3):319-330. doi: 10.1007/s12079-018-0492-0

 

  1. Suzuki Y, Shirai M, Asada K, et al. Macrophage mannose receptor, CD206, predict prognosis in patients with pulmonary tuberculosis. Sci Rep. 2018;8(1):13129. doi: 10.1038/s41598-018-31565-5

 

  1. Garcia-Aguilar T, Espinosa-Cueto P, Magallanes-Puebla A, Mancilla R. The mannose receptor is involved in the phagocytosis of mycobacteria-induced apoptotic cells. J Immunol Res. 2016;2016:3845247. doi: 10.1155/2016/3845247

 

  1. Fu CP, Cai XY, Chen SL, et al. Hyaluronic acid-based nanocarriers for anticancer drug delivery. Polymers (Basel). 2023;15(10):2317. doi: 10.3390/polym15102317

 

  1. Zhao X, Li H, Lee RJ. Targeted drug delivery via folate receptors. Expert Opin Drug Deliv. 2008;5(3):309-319. doi: 10.1517/17425247.5.3.309

 

  1. Sudimack J, Lee RJ. Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev. 2000;41(2):147-162. doi: 10.1016/s0169-409x(99)00062-9

 

  1. Chen S, Zhao X, Chen J, et al. Mechanism-based tumor-targeting drug delivery system. Validation of efficient vitamin receptor-mediated endocytosis and drug release. Bioconjug Chem. 2010;21(5):979-987. doi: 10.1021/bc9005656

 

  1. Liang Y, Tian B, Zhang J, et al. Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer. Int J Nanomedicine. 2017;12:1699-1715. doi: 10.2147/ijn.S121262

 

  1. Tavares Luiz M, Delello Di Filippo L, Carolina Alves R, et al. The use of TPGS in drug delivery systems to overcome biological barriers. Eur Polym J. 2021;142:110129. doi: 10.1016/j.eurpolymj.2020.110129

 

  1. Zhang Z, Tan S, Feng SS. Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials. 2012;33(19):4889-4906. doi: 10.1016/j.biomaterials.2012.03.046

 

  1. Du J, Li L. Which one performs better for targeted lung cancer combination therapy: Pre- or post-bombesin-decorated nanostructured lipid carriers? Drug Deliv. 2016;23(5):1799-1809. doi: 10.3109/10717544.2015.1099058

 

  1. Jain S, Amiji M. Tuftsin-modified alginate nanoparticles as a noncondensing macrophage-targeted DNA delivery system. Biomacromolecules. 2012;13(4):1074-1085. doi: 10.1021/bm2017993

 

  1. Han CY, Yue LL, Tai LY, et al. A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro. Int J Nanomedicine. 2013;8:1541-1549. doi: 10.2147/ijn.S43627

 

  1. Zhou J, Sun M, Jin S, et al. Combined using of paclitaxel and salinomycin active targeting nanostructured lipid carriers against non-small cell lung cancer and cancer stem cells. Drug Deliv. 2019;26(1):281-289. doi: 10.1080/10717544.2019.1580799

 

  1. Movafegh B, Jalal R, Mohammadi Z, Aldaghi SA. Poly-L-arginine: Enhancing cytotoxicity and cellular uptake of doxorubicin and necrotic cell death. Anticancer Agents Med Chem. 2018;18(10):1448-1456. doi: 10.2174/1871520618666180412114750

 

  1. Hädrich G, Vaz GR, Bidone J, et al. Development of a novel lipid-based nanosystem functionalized with WGA for enhanced intracellular drug delivery. Pharmaceutics. 2022;14(10):2022. doi: 10.3390/pharmaceutics14102022

 

  1. Qian ZM, Li H, Sun H, Ho K. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev. 2002;54(4):561-587. doi: 10.1124/pr.54.4.561

 

  1. Daniels TR, Bernabeu E, Rodríguez JA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta. 2012;1820(3):291-317. doi: 10.1016/j.bbagen.2011.07.016

 

  1. Lara-Guerra H, Roth JA. Gene therapy for lung cancer. Crit Rev Oncog. 2016;21(1-2):115-124. doi: 10.1615/CritRevOncog.2016016084

 

  1. Li S, Chen L, Wang G, et al. Anti-ICAM-1 antibody-modified nanostructured lipid carriers: A pulmonary vascular endothelium-targeted device for acute lung injury therapy. J Nanobiotechnology. 2018;16(1):105. doi: 10.1186/s12951-018-0431-5

 

  1. Arslan FB, Ozturk K, Calis S. Antibody-mediated drug delivery. Int J Pharm. 2021;596:120268. doi: 10.1016/j.ijpharm.2021.120268

 

  1. Wathoni N, Puluhulawa LE, Joni IM, et al. Monoclonal antibody as a targeting mediator for nanoparticle targeted delivery system for lung cancer. Drug Deliv. 2022;29(1):2959-2970. doi: 10.1080/10717544.2022.2120566

 

  1. Guo S, Zhang Y, Wu Z, et al. Synergistic combination therapy of lung cancer: Cetuximab functionalized nanostructured lipid carriers for the co-delivery of paclitaxel and 5-Demethylnobiletin. Biomed Pharmacother. 2019;118:109225. doi: 10.1016/j.biopha.2019.109225

 

  1. Zhuo S, Zhang F, Yu J, Zhang X, Yang G, Liu X. pH-sensitive biomaterials for drug delivery. Molecules. 2020;25(23):5649. doi: 10.3390/molecules25235649

 

  1. Zhao Z, Ukidve A, Kim J, Mitragotri S. Targeting strategies for tissue-specific drug delivery. Cell. 2020;181(1):151-167. doi: 10.1016/j.cell.2020.02.001

 

  1. Morshed M, Chowdhury EH. Gene delivery and clinical applications. In: Narayan R, editor. Encyclopedia of Biomedical Engineering. Netherlands: Elsevier; 2019. p. 345-351.

 

  1. Zhang X, Gan Y, Gan L, Nie S, Pan W. PEGylated nanostructured lipid carriers loaded with 10-hydroxycamptothecin: An efficient carrier with enhanced anti-tumour effects against lung cancer. J Pharm Pharmacol. 2008;60(8):1077-1087. doi: 10.1211/jpp.60.8.0014

 

  1. Du M, Yin J. Dual-drug nanosystem: Etoposide prodrug and cisplatin coloaded nanostructured lipid carriers for lung cancer therapy. Drug Des Devel Ther. 2022;16:4139-4149. doi: 10.2147/dddt.S386100

 

  1. Bondì ML, Ferraro M, Di Vincenzo S, et al. Effects in cigarette smoke stimulated bronchial epithelial cells of a corticosteroid entrapped into nanostructured lipid carriers. J Nanobiotechnology. 2014;12:46. doi: 10.1186/s12951-014-0046-4

 

  1. Shadambikar G, Marathe S, Ji N, et al. Formulation development of itraconazole PEGylated nano-lipid carriers for pulmonary aspergillosis using hot-melt extrusion technology. Int J Pharm X. 2021;3:100074. doi: 10.1016/j.ijpx.2021.100074

 

  1. Garbuzenko OB, Kbah N, Kuzmov A, Pogrebnyak N, Pozharov V, Minko T. Inhalation treatment of cystic fibrosis with lumacaftor and ivacaftor co-delivered by nanostructured lipid carriers. J Control Release. 2019;296:225-231. doi: 10.1016/j.jconrel.2019.01.025

 

  1. Magalhães J, Pinheiro M, Drasler B, et al. Lipid nanoparticles biocompatibility and cellular uptake in a 3D human lung model. Nanomedicine (Lond). 2020;15(3):259-271. doi: 10.2217/nnm-2019-0256

 

  1. Patil TS, Deshpande AS. Nanostructured lipid carrier-mediated lung targeted drug delivery system to enhance the safety and bioavailability of clofazimine. Drug Dev Ind Pharm. 2021;47(3):385-393. doi: 10.1080/03639045.2021.1892743

 

  1. Pinheiro M, Ribeiro R, Vieira A, Andrade F, Reis S. Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis. Drug Des Devel Ther. 2016;10:2467-2475. doi: 10.2147/dddt.S104395

 

  1. Song X, Lin Q, Guo L, et al. Rifampicin loaded mannosylated cationic nanostructured lipid carriers for alveolar macrophage-specific delivery. Pharm Res. 2015;32(5):1741-1751. doi: 10.1007/s11095-014-1572-3

 

  1. Zhang B, Zhang Y, Yu D. Lung cancer gene therapy: Transferrin and hyaluronic acid dual ligand-decorated novel lipid carriers for targeted gene delivery. Oncol Rep. 2017;37(2):937-944. doi: 10.3892/or.2016.5298

 

  1. Ma Y, Liu J, Cui X, et al. Hyaluronic acid modified nanostructured lipid carrier for targeting delivery of kaempferol to NSCLC: Preparation, optimization, characterization, and performance evaluation in vitro. Molecules. 2022;27(14):4553. doi: 10.3390/molecules27144553

 

  1. Mahmoudi S, Ghorbani M, Sabzichi M, Ramezani F, Hamishehkar H, Samadi N. Targeted hyaluronic acid-based lipid nanoparticle for apigenin delivery to induce Nrf2-dependent apoptosis in lung cancer cells. J Drug Deliv Sci Technol. 2019;49:268-276. doi: 10.1016/j.jddst.2018.11.013

 

  1. Wannas AN, Mahdi MF, Maraie NK. Unraveling the role of hyaluronic acid on the targeting of vinorelbine-loaded NLC for lung cancer. Pharmacia. 2025;72:1-13. doi: 10.3897/pharmacia.72.e143192

 

  1. Ucar E, Teksoz S, Ichedef C, et al. Synthesis, characterization and radiolabeling of folic acid modified nanostructured lipid carriers as a contrast agent and drug delivery system. Appl Radiat Isotopes. 2017;119:72-79. doi: 10.1016/j.apradiso.2016.11.002

 

  1. Rajoriya V, Gupta R, Vengurlekar S, Jain SK. Folate conjugated Nano- Lipid construct of Paclitaxel for site-specific lung squamous carcinoma targeting. Int J Pharm. 2025;672:125312. doi: 10.1016/j.ijpharm.2025.125312

 

  1. Rawal S, Bora V, Patel B, Patel M. Surface-engineered nanostructured lipid carrier systems for synergistic combination oncotherapy of non-small cell lung cancer. Drug Deliv Transl Res. 2021;11(5):2030-2051. doi: 10.1007/s13346-020-00866-6

 

  1. Taymouri S, Alem M, Varshosaz J, Rostami M, Akbari V, Firoozpour L. Biotin decorated sunitinib loaded nanostructured lipid carriers for tumor targeted chemotherapy of lung cancer. J Drug Deliv Sci Technol. 2019;50:237-247. doi: 10.1016/j.jddst.2019.01.024

 

  1. Sherif AY, Harisa GI, Alanazi FK, Nasr FA, Alqahtani AS. Engineered nanoscale lipid-based formulation as potential enhancer of gefitinib lymphatic delivery: Cytotoxicity and apoptotic studies against the A549 cell line. AAPS PharmSciTech. 2022;23(6):183. doi: 10.1208/s12249-022-02332-7

 

  1. Carneiro SP, Carvalho KV, de Oliveira Aguiar Soares RD, et al. Functionalized rifampicin-loaded nanostructured lipid carriers enhance macrophages uptake and antimycobacterial activity. Colloids Surf B Biointerfaces. 2019;175:306-313. doi: 10.1016/j.colsurfb.2018.12.003

 

  1. Sun M, Gao Y, Zhu Z, et al. A systematic in vitro investigation on poly-arginine modified nanostructured lipid carrier: Pharmaceutical characteristics, cellular uptake, mechanisms and cytotoxicity. Asian J Pharm Sci. 2017;12(1):51-58. doi: 10.1016/j.ajps.2016.07.007

 

  1. Shao Z, Shao J, Tan B, et al. Targeted lung cancer therapy: Preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA. Int J Nanomedicine. 2015;10:1223-1233. doi: 10.2147/ijn.S77837

 

  1. Han Y, Li Y, Zhang P, et al. Nanostructured lipid carriers as novel drug delivery system for lung cancer gene therapy. Pharm Dev Technol. 2016;21(3):277-281. doi: 10.3109/10837450.2014.996900

 

  1. Han Y, Zhang Y, Li D, Chen Y, Sun J, Kong F. Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin. Int J Nanomedicine. 2014;9:4107-4116. doi: 10.2147/ijn.S67770

 

  1. Garbuzenko OB, Ivanova V, Kholodovych V, et al. Combinatorial treatment of idiopathic pulmonary fibrosis using nanoparticles with prostaglandin E and siRNA(s). Nanomedicine. 2017;13(6):1983-1992. doi: 10.1016/j.nano.2017.04.005

 

  1. Taratula O, Kuzmov A, Shah M, Garbuzenko OB, Minko T. Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J Control Release. 2013;171(3):349-357. doi: 10.1016/j.jconrel.2013.04.018

 

  1. Islan GA, Tornello PC, Abraham GA, Duran N, Castro GR. Smart lipid nanoparticles containing levofloxacin and DNase for lung delivery. Design and characterization. Colloids Surf B Biointerfaces. 2016;143:168-176. doi: 10.1016/j.colsurfb.2016.03.040

 

  1. Li SJ, Wang XJ, Hu JB, et al. Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy. Drug Deliv. 2017;24(1):402-413. doi: 10.1080/10717544.2016.1259369

 

  1. Cao C, Wang Q, Liu Y. Lung cancer combination therapy: Doxorubicin and β-elemene co-loaded, pH-sensitive nanostructured lipid carriers. Drug Des Devel Ther. 2019;13:1087-1098. doi: 10.2147/dddt.S198003

 

  1. Taher M, Susanti D, Haris MS, et al. PEGylated liposomes enhance the effect of cytotoxic drug: A review. Heliyon. 2023;9(3):e13823. doi: 10.1016/j.heliyon.2023.e13823

 

  1. Mohamed M, Abu Lila AS, Shimizu T, et al. PEGylated liposomes: Immunological responses. Sci Technol Adv Mater. 2019;20(1):710-724. doi: 10.1080/14686996.2019.1627174

 

  1. Nosova AS, Koloskova OO, Nikonova AA, et al. Diversity of PEGylation methods of liposomes and their influence on RNA delivery. Medchemcomm. 2019;10(3):369-377. doi: 10.1039/c8md00515j

 

  1. Barenholz Y. Doxil® — The first FDA-approved nano-drug: Lessons learned. J Control Release. 2012;160(2):117-134. doi: 10.1016/j.jconrel.2012.03.020

 

  1. Dellapasqua S, Trillo Aliaga P, Munzone E, et al. Pegylated liposomal doxorubicin (Caelyx(®)) as adjuvant treatment in early-stage luminal B-like breast cancer: A feasibility phase II trial. Curr Oncol. 2021;28(6):5167-5178. doi: 10.3390/curroncol28060433

 

  1. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. 2016;99(Pt A):28-51. doi: 10.1016/j.addr.2015.09.012

 

  1. Fan W, Peng H, Yu Z, et al. The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers. Acta Pharm Sin B. 2022;12(5):2479-2493. doi: 10.1016/j.apsb.2021.11.016

 

  1. Salmaso S, Caliceti P. Stealth properties to improve therapeutic efficacy of drug nanocarriers. J Drug Deliv. 2013;2013:374252. doi: 10.1155/2013/374252

 

  1. Verhoef JJ, Anchordoquy TJ. Questioning the use of PEGylation for drug delivery. Drug Deliv Transl Res. 2013;3(6):499-503. doi: 10.1007/s13346-013-0176-5

 

  1. Shi D, Beasock D, Fessler A, et al. To PEGylate or not to PEGylate: Immunological properties of nanomedicine’s most popular component, polyethylene glycol and its alternatives. Adv Drug Deliv Rev. 2022;180:114079. doi: 10.1016/j.addr.2021.114079

 

  1. Simberg D, Barenholz Y, Roffler SR, Landfester K, Kabanov AV, Moghimi SM. PEGylation technology: Addressing concerns, moving forward. Drug Deliv. 2025;32(1):2494775. doi: 10.1080/10717544.2025.2494775

 

  1. Peng P, Yang K, Tong G, Ma L. Polysaccharide nanoparticles for targeted cancer therapies. Curr Drug Metab. 2018;19(9):781-792. doi: 10.2174/1389200219666180511153403

 

  1. Kang PB, Azad AK, Torrelles JB, et al. The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J Exp Med. 2005;202(7):987-999. doi: 10.1084/jem.20051239

 

  1. Rajaram MVS, Arnett E, Azad AK, et al. M. tuberculosis-initiated human mannose receptor signaling regulates macrophage recognition and vesicle trafficking by FcRγ-Chain, Grb2, and SHP-1. Cell Rep. 2017;21(1):126-140. doi: 10.1016/j.celrep.2017.09.034

 

  1. Ahmad F, Rani A, Alam A, et al. Macrophage: A cell with many faces and functions in tuberculosis. Front Immunol. 2022;13:747799. doi: 10.3389/fimmu.2022.747799

 

  1. Guirado E, Schlesinger LS, Kaplan G. Macrophages in tuberculosis: Friend or foe. Semin Immunopathol. 2013;35(5):563-583. doi: 10.1007/s00281-013-0388-2

 

  1. Rajaram MVS, Brooks MN, Morris JD, Torrelles JB, Azad AK, Schlesinger LS. Mycobacterium tuberculosis activates human macrophage peroxisome proliferator-activated receptor γ linking mannose receptor recognition to regulation of immune responses. J Immunol. 2010;185(2):929-942. doi: 10.4049/jimmunol.1000866

 

  1. Tucak-Smajić A, Ruseska I, Letofsky-Papst I, Vranić E, Zimmer A. Development and characterization of cationic nanostructured lipid carriers as drug delivery systems for miRNA-27a. Pharmaceuticals (Basel). 2023;16(7):1007. doi: 10.3390/ph16071007

 

  1. Zhao F, Nayyar D, Hwang YS, Bartucci R, Salvati A. Effect of positive charges on liposome stability, uptake efficacy and impact on cells. Int J Pharm. 2025;681:125881. doi: 10.1016/j.ijpharm.2025.125881

 

  1. Hald Albertsen C, Kulkarni JA, Witzigmann D, Lind M, Petersson K, Simonsen JB. The role of lipid components in lipid nanoparticles for vaccines and gene therapy. Adv Drug Deliv Rev. 2022;188:114416. doi: 10.1016/j.addr.2022.114416

 

  1. van der Zande HJP, Nitsche D, Schlautmann L, Guigas B, Burgdorf S. The mannose receptor: From endocytic receptor and biomarker to regulator of (meta)inflammation. Review. Front Immunol. 2021;12:765034. doi: 10.3389/fimmu.2021.765034

 

  1. Bai L, Chen X, Li C, et al. Mannose/stearyl chloride doubly functionalized polyethylenimine as a nucleic acid vaccine carrier to promote macrophage uptake. Drug Deliv. 2024;31(1):2427138. doi: 10.1080/10717544.2024.2427138

 

  1. Huang G, Huang H. Application of hyaluronic acid as carriers in drug delivery. Drug Deliv. 2018;25(1):766-772. doi: 10.1080/10717544.2018.1450910

 

  1. Luo Z, Dai Y, Gao H. Development and application of hyaluronic acid in tumor targeting drug delivery. Acta Pharm Sin B. 2019;9(6):1099-1112. doi: 10.1016/j.apsb.2019.06.004

 

  1. Huang G, Huang H. Hyaluronic acid-based biopharmaceutical delivery and tumor-targeted drug delivery system. J Control Release. 2018;278:122-126. doi: 10.1016/j.jconrel.2018.04.015

 

  1. Qhattal HS, Liu X. Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes. Mol Pharm. 2011;8(4):1233-1246. doi: 10.1021/mp2000428

 

  1. Yin T, Liu J, Zhao Z, et al. Smart nanoparticles with a detachable outer shell for maximized synergistic antitumor efficacy of therapeutics with varying physicochemical properties. J Control Release. 2016;243:54-68. doi: 10.1016/j.jconrel.2016.09.036

 

  1. Pashkina E, Bykova M, Berishvili M, Lazarev Y, Kozlov V. Hyaluronic acid-based drug delivery systems for cancer therapy. Cells. 2025;14(2):61. doi: 10.3390/cells14020061

 

  1. Pei D, Buyanova M. Overcoming endosomal entrapment in drug delivery. Bioconjug Chem. 2019;30(2):273-283. doi: 10.1021/acs.bioconjchem.8b00778

 

  1. Wang C, Xiu Y, Zhang Y, et al. Recent advances in biotin-based therapeutic agents for cancer therapy. 10.1039/D4NR03729D. Nanoscale. 2025;17(4):1812-1873. doi: 10.1039/D4NR03729D

 

  1. Lesch HP, Kaikkonen MU, Pikkarainen JT, Ylä-Herttuala S. Avidin-biotin technology in targeted therapy. Expert Opin Drug Deliv. 2010;7(5):551-564. doi: 10.1517/17425241003677749

 

  1. Cheung A, Bax HJ, Josephs DH, et al. Targeting folate receptor alpha for cancer treatment. Oncotarget. 2016;7(32):52553-52574. doi: 10.18632/oncotarget.9651

 

  1. Jones SK, Sarkar A, Feldmann DP, Hoffmann P, Merkel OM. Revisiting the value of competition assays in folate receptor-mediated drug delivery. Biomaterials. 2017;138:35-45. doi: 10.1016/j.biomaterials.2017.05.034

 

  1. Thabet RH, Alessa REM, Al-Smadi ZKK, et al. Folic acid: Friend or foe in cancer therapy. J Int Med Res. 2024;52(1):3000605231223064. doi: 10.1177/03000605231223064

 

  1. Bandara NA, Hansen MJ, Low PS. Effect of receptor occupancy on folate receptor internalization. Mol Pharm. 2014;11(3):1007-1013. doi: 10.1021/mp400659t

 

  1. Tripathi R, Guglani A, Ghorpade R, Wang B. Biotin conjugates in targeted drug delivery: Is it mediated by a biotin transporter, a yet to be identified receptor, or (an)other unknown mechanism(s)? J Enzyme Inhib Med Chem. 2023;38(1):2276663. doi: 10.1080/14756366.2023.2276663

 

  1. Pliszka M, Szablewski L. Glucose transporters as a target for anticancer therapy. Cancers (Basel). 2021;13(16):4184. doi: 10.3390/cancers13164184

 

  1. Augustin R. The protein family of glucose transport facilitators: It’s not only about glucose after all. IUBMB Life. 2010;62(5):315-33. doi: 10.1002/iub.315

 

  1. Zhang X, Lu JJ, Abudukeyoumu A, et al. Glucose transporters: Important regulators of endometrial cancer therapy sensitivity. Review. Front Oncol. 2022;12:933827. doi: 10.3389/fonc.2022.933827

 

  1. Han S, Mallampalli RK. The role of surfactant in lung disease and host defense against pulmonary infections. Ann Am Thorac Soc. 2015;12(5):765-774. doi: 10.1513/AnnalsATS.201411-507FR

 

  1. Morales JO, Peters JI, Williams RO 3rd. Surfactants: Their critical role in enhancing drug delivery to the lungs. Ther Deliv. 2011;2(5):623-641. doi: 10.4155/tde.11.15

 

  1. Abdullah S, Mukherjee S, Shweta, Debnath B. The prevention of multi-drug resistance in cancers through the application of nanotechnology-based targeted delivery systems for combination therapies involving traditional Chinese medicine. Pharmacol Res Modern Chin Med. 2024;10:100386. doi: 10.1016/j.prmcm.2024.100386

 

  1. Yang C, Wu T, Qi Y, Zhang Z. Recent advances in the application of vitamin E TPGS for drug delivery. Theranostics. 2018;8(2):464-485. doi: 10.7150/thno.22711

 

  1. Mehata AK, Setia A, Vikas, et al. Vitamin E TPGS-Based nanomedicine, nanotheranostics, and targeted drug delivery: Past, present, and future. Pharmaceutics. 2023;15(3):722. doi: 10.3390/pharmaceutics15030722

 

  1. Nagaraj K. Surfactant-based drug delivery systems for cancer therapy: Advances, challenges, and future perspectives. Int J Pharm. 2025;679:125655. doi: 10.1016/j.ijpharm.2025.125655

 

  1. Baer B, Souza LMP, Pimentel AS, Veldhuizen RAW. New insights into exogenous surfactant as a carrier of pulmonary therapeutics. Biochem Pharmacol. 2019;164:64-73. doi: 10.1016/j.bcp.2019.03.036

 

  1. Berillo D, Yeskendir A, Zharkinbekov Z, Raziyeva K, Saparov A. Peptide-based drug delivery systems. Medicina (Kaunas). 2021;57(11):1209. doi: 10.3390/medicina57111209

 

  1. Todaro B, Ottalagana E, Luin S, Santi M. Targeting peptides: The new generation of targeted drug delivery systems. Pharmaceutics. 2023;15(6):1648. doi: 10.3390/pharmaceutics15061648

 

  1. Barve A, Jin W, Cheng K. Prostate cancer relevant antigens and enzymes for targeted drug delivery. J Control Release. 2014;187:118-132. doi: 10.1016/j.jconrel.2014.05.035

 

  1. Akhtar MJ, Ahamed M, Alhadlaq HA, Alrokayan SA, Kumar S. Targeted anticancer therapy: Overexpressed receptors and nanotechnology. Clin Chim Acta. 2014;436:78-92. doi: 10.1016/j.cca.2014.05.004

 

  1. Khan MA. Targeted drug delivery using tuftsin-bearing liposomes: Implications in the treatment of infectious diseases and tumors. Curr Drug Targets. 2021;22(7):770-778. doi: 10.2174/1389450121999201125200756

 

  1. Khairkhah N, Namvar A, Bolhassani A. Application of cell penetrating peptides as a promising drug carrier to combat viral infections. Mol Biotechnol. 2023;65(9):1387-1402. doi: 10.1007/s12033-023-00679-1

 

  1. Sun Z, Huang J, Fishelson Z, Wang C, Zhang S. Cell-penetrating peptide-based delivery of macromolecular drugs: Development, strategies, and progress. Biomedicines. 2023;11(7):1971. doi: 10.3390/biomedicines11071971

 

  1. Kotadiya DD, Patel P, Patel HD. Cell-penetrating peptides: A powerful tool for targeted drug delivery. Curr Drug Deliv. 2023;21:368-388. doi: 10.2174/1567201820666230407092924

 

  1. Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv. 2013;4(11):1443-67. doi: 10.4155/tde.13.104

 

  1. Shi M, McHugh KJ. Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems. Adv Drug Deliv Rev. 2023;199:114904. doi: 10.1016/j.addr.2023.114904

 

  1. Qin L, Cui Z, Wu Y, et al. Challenges and strategies to enhance the systemic absorption of inhaled peptides and proteins. Pharm Res. 2023;40(5):1037-1055. doi: 10.1007/s11095-022-03435-3

 

  1. Wang Y, Zhang L, Liu C, Luo Y, Chen D. Peptide-mediated nanocarriers for targeted drug delivery: Developments and strategies. Pharmaceutics. 2024;16(2):240. doi: 10.3390/pharmaceutics16020240

 

  1. Wu J, Sahoo JK, Li Y, Xu Q, Kaplan DL. Challenges in delivering therapeutic peptides and proteins: A silk-based solution. J Control Release. 2022;345:176-189. doi: 10.1016/j.jconrel.2022.02.011

 

  1. Xiao Y, Liu P, Wei J, Zhang X, Guo J, Lin Y. Recent progress in targeted therapy for non-small cell lung cancer. Review. Front Pharmacol. 2023;14:1125547. doi: 10.3389/fphar.2023.1125547

 

  1. Dana H, Chalbatani GM, Mahmoodzadeh H, et al. Molecular mechanisms and biological functions of siRNA. Int J Biomed Sci. 2017;13(2):48-57.

 

  1. Creixell M, Peppas NA. Co-delivery of siRNA and therapeutic agents using nanocarriers to overcome cancer resistance. Nano Today. 2012;7(4):367-379. doi: 10.1016/j.nantod.2012.06.013

 

  1. Ahsan A, Thomas N, Barnes TJ, et al. Lipid nanocarriers-enabled delivery of antibiotics and antimicrobial adjuvants to overcome bacterial biofilms. Pharmaceutics. 2024;16(3):396. doi: 10.3390/pharmaceutics16030396

 

  1. Baelo A, Levato R, Julián E, et al. Disassembling bacterial extracellular matrix with DNase-coated nanoparticles to enhance antibiotic delivery in biofilm infections. J Control Release. 2015;209:150-158. doi: 10.1016/j.jconrel.2015.04.028

 

  1. Ali Zaidi SS, Fatima F, Ali Zaidi SA, Zhou D, Deng W, Liu S. Engineering siRNA therapeutics: Challenges and strategies. J Nanobiotechnology. 2023;21(1):381. doi: 10.1186/s12951-023-02147-z

 

  1. Reischl D, Zimmer A. Drug delivery of siRNA therapeutics: Potentials and limits of nanosystems. Nanomedicine. 2009;5(1):8-20. doi: 10.1016/j.nano.2008.06.001

 

  1. Sajid MI, Moazzam M, Kato S, Yeseom Cho K, Tiwari RK. Overcoming barriers for siRNA therapeutics: From bench to bedside. Pharmaceuticals (Basel). 2020;13(10):294. doi: 10.3390/ph13100294

 

  1. Awwad S, Angkawinitwong U. Overview of antibody drug delivery. Pharmaceutics. 2018;10(3):83. doi: 10.3390/pharmaceutics10030083

 

  1. Huynh U, Wu P, Qiu J, et al. Targeted drug delivery using a plug-to-direct antibody-nanogel conjugate. Biomacromolecules. 2023;24(2):849-857. doi: 10.1021/acs.biomac.2c01269

 

  1. Chen Z, Kankala RK, Yang Z, et al. Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects. Theranostics. 2022;12(8):3719-3746. doi: 10.7150/thno.72594

 

  1. Slastnikova TA, Ulasov AV, Rosenkranz AA, Sobolev AS. Targeted intracellular delivery of antibodies: The state of the art. Review. Front Pharmacol. 2018;9:208. doi: 10.3389/fphar.2018.01208

 

  1. Buyukgolcigezli I, Tenekeci AK, Sahin IH. Opportunities and challenges in antibody-drug conjugates for cancer therapy: A new era for cancer treatment. Cancers (Basel). 2025;17(6):958. doi: 10.3390/cancers17060958

 

  1. Thurber GM, Schmidt MM, Wittrup KD. Factors determining antibody distribution in tumors. Trends Pharmacol Sci. 2008;29(2):57-61. doi: 10.1016/j.tips.2007.11.004

 

  1. Flugel CL, Majzner RG, Krenciute G, et al. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. Nat Rev Clin Oncol. 2023;20(1):49-62. doi: 10.1038/s41571-022-00704-3

 

  1. Loganzo F, Sung M, Gerber HP. Mechanisms of resistance to antibody-drug conjugates. Mol Cancer Ther. 2016;15(12):2825-2834. doi: 10.1158/1535-7163.Mct-16-0408

 

  1. Zahavi D, Weiner L. Monoclonal antibodies in cancer therapy. Antibodies (Basel). 2020;9(3):34. doi: 10.3390/antib9030034

 

  1. Huh KM, Kang HC, Lee YJ, Bae YH. pH-sensitive polymers for drug delivery. Macromol Res. 2012;20(3):224-233. doi: 10.1007/s13233-012-0059-5

 

  1. Mu Y, Gong L, Peng T, Yao J, Lin Z. Advances in pH-responsive drug delivery systems. OpenNano. 2021;5:100031. doi: 10.1016/j.onano.2021.100031

 

  1. Ghaffar A, Yameen B, Latif M, Malik MI. pH-sensitive drug delivery systems. In: Shah MR, Imran M, Ullah S, editors. Metal Nanoparticles for Drug Delivery and Diagnostic Applications. Ch. 14. Netherlands: Elsevier; 2020. p. 259-278.

 

  1. Sonawane SJ, Kalhapure RS, Govender T. Hydrazone linkages in pH responsive drug delivery systems. Eur J Pharm Sci. 2017;99:45-65. doi: 10.1016/j.ejps.2016.12.011

 

  1. Kölmel DK, Kool ET. Oximes and hydrazones in bioconjugation: Mechanism and catalysis. Chem Rev. 2017;117(15):10358-10376. doi: 10.1021/acs.chemrev.7b00090

 

  1. Gannimani R, Walvekar P, Naidu VR, Aminabhavi TM, Govender T. Acetal containing polymers as pH-responsive nano-drug delivery systems. J Control Release. 2020;328:736-761. doi: 10.1016/j.jconrel.2020.09.044

 

  1. Sun L, Liu H, Ye Y, et al. Smart nanoparticles for cancer therapy. Signal Transduct Target Ther. 2023;8(1):418. doi: 10.1038/s41392-023-01642-x

 

  1. Chu S, Shi X, Tian Y, Gao F. pH-responsive polymer nanomaterials for tumor therapy. Front Oncol. 2022;12:855019. doi: 10.3389/fonc.2022.855019

 

  1. Tang H, Zhao W, Yu J, Li Y, Zhao C. Recent development of pH-responsive polymers for cancer nanomedicine. Molecules. 2019;24(1):4. doi: 10.3390/molecules24010004

 

  1. Yang X, Pan Z, Choudhury MR, et al. Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery. Med Res Rev. 2020;40(6):2682-2713. doi: 10.1002/med.21720

 

  1. Verkhovskii RA, Ivanov AN, Lengert EV, Tulyakova KA, Shilyagina NY, Ermakov AV. Current principles, challenges, and new metrics in pH-responsive drug delivery systems for systemic cancer therapy. Pharmaceutics. 2023;15(5):1566. doi: 10.3390/pharmaceutics15051566

 

  1. Cao Z, Li W, Liu R, et al. pH- and enzyme-triggered drug release as an important process in the design of anti-tumor drug delivery systems. Biomed Pharmacother. 2019;118:109340. doi: 10.1016/j.biopha.2019.109340

 

  1. Haque S, Whittaker MR, McIntosh MP, Pouton CW, Kaminskas LM. Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges. Nanomedicine. 2016;12(6):1703-1724. doi: 10.1016/j.nano.2016.03.002

 

  1. Guo Y, Bera H, Shi C, Zhang L, Cun D, Yang M. Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines. Acta Pharm Sin B. 2021;11(8):2565-2584. doi: 10.1016/j.apsb.2021.05.015

 

  1. Zito Marino F, Bianco R, Accardo M, et al. Molecular heterogeneity in lung cancer: from mechanisms of origin to clinical implications. Int J Med Sci. 2019;16(7):981-989. doi: 10.7150/ijms.34739

 

  1. Garbuzenko OB, Kuzmov A, Taratula O, Pine SR, Minko T. Strategy to enhance lung cancer treatment by five essential elements: Inhalation delivery, nanotechnology, tumor-receptor targeting, chemo- and gene therapy. Theranostics. 2019;9(26):8362-8376. doi: 10.7150/thno.39816

 

  1. Dhiman N, Awasthi R, Sharma B, Kharkwal H, Kulkarni GT. Lipid nanoparticles as carriers for bioactive delivery. Review. Front Chem. 2021;9:580118. doi: 10.3389/fchem.2021.580118

 

  1. Khanna P, Ong C, Bay BH, Baeg GH. Nanotoxicity: An interplay of oxidative stress, inflammation and cell death. Nanomaterials (Basel). 2015;5(3):1163-1180. doi: 10.3390/nano5031163

 

  1. Zhang S, Li R, Jiang T, et al. Inhalable nanomedicine for lung cancer treatment. Smart Mater Med. 2024;5(2):261-280. doi: 10.1016/j.smaim.2024.04.001

 

  1. Hargrave KE, MacLeod MKL, Worrell JC. Antigen presenting cells: Professionals, amateurs, and spectators in the “long game” of lung immunity. Int J Biochem Cell Biol. 2022;153:106331. doi: 10.1016/j.biocel.2022.106331

 

  1. Dey AK, Nougarède A, Clément F, et al. Tuning the immunostimulation properties of cationic lipid nanocarriers for nucleic acid delivery. Front Immunol. 2021;12:722411. doi: 10.3389/fimmu.2021.722411

 

  1. Swami R, Popli P, Sal K, et al. A review on biomacromolecular ligand-directed nanoparticles: New era in macrophage targeting. Int J Biol Macromol. 2025;306:141740. doi: 10.1016/j.ijbiomac.2025.141740

 

  1. United States National Library of Medicine. ImmunityBio I. THEMBA II T-Cell vaccine: Vaccination with saRNA COVID-19 Vaccines NCT05370040 [Internet]. National Institutes of Health. 2025. Available from: https://clinicaltrials.gov/study/NCT05370040 [Last accessed on 2025 Aug 08].

 

  1. Rice A, Verma M, Voigt E, et al. Heterologous saRNA prime, DNA dual-antigen boost SARS-CoV-2 vaccination elicits robust cellular immunogenicity and cross-variant neutralizing antibodies. Original Research. Front Immunol. 2022;13:910136. doi: 10.3389/fimmu.2022.910136

 

  1. Jennewein MF, Schultz MD, Beaver S, Battisti P, Bakken J, Hanson D, et al. Intranasal self-amplifying RNA SARS-CoV-2 vaccine produces protective respiratory and systemic immunity and prevents viral transmission. bioRxiv. 2024:2022.11.10.515993. doi: 10.1101/2022.11.10.515993

 

  1. Voigt EA, Gerhardt A, Hanson D, et al. A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability. NPJ Vaccines. 2022;7(1):136. doi: 10.1038/s41541-022-00549-y

 

  1. Berz D, Jotte RM, Pachipala KK, Spira AI, Berger MS. ACCLAIM-1 dose escalation: Determination of quaratusugene ozeplasmid and osimertinib recommended phase 2 dose (RP2D). J Clin Oncol. 2023;41(16_suppl):e15081. doi: 10.1200/JCO.2023.41.16_suppl.e15081

 

  1. United States National Library of Medicine. Genprex I. Quaratusugene Ozeplasmid (Reqorsa) and Atezolizumab Maintenance Therapy in ES-SCLC Patients (Acclaim-3) NCT05703971 [Internet]. National Institutes of Health. 2025. Available from: https://www.clinicaltrials. gov/study/NCT05703971 [Last accessed on 2025 Aug 08].

 

  1. Costabile G, Conte G, Brusco S, et al. State-of-the-art review on inhalable lipid and polymer nanocarriers: Design and development perspectives. Pharmaceutics. 2024;16(3):347. doi: 10.3390/pharmaceutics16030347

 

  1. United States National Library of Medicine. Arcturus Therapeutics I. Data from: Safety, Tolerability and Efficacy Study of ARCT-032 in People with Cystic Fibrosis (LunairCF) NCT06747858 [Internet]. National Institutes of Health. 2025. Available from: https://www. clinicaltrials.gov/study/NCT06747858 [Last accessed on 2025 Aug 08].

 

  1. Han JP, Kim M, Choi BS, et al. In vivo delivery of CRISPR-Cas9 using lipid nanoparticles enables antithrombin gene editing for sustainable hemophilia A and B therapy. Sci Adv. 2022;8(3):eabj6901. doi: 10.1126/sciadv.abj6901

 

  1. Wu F, Li N, Xiao Y, et al. Lipid nanoparticles for delivery of CRISPR gene editing components. Small Methods. 2025:2401632. doi: 10.1002/smtd.202401632

 

  1. Li H, Zhao Y, Xu C. Machine learning techniques for lipid nanoparticle formulation. Nano Converg. 2025;12(1):35. doi: 10.1186/s40580-025-00502-4

 

  1. Cheng L, Zhu Y, Ma J, et al. Machine learning elucidates design features of plasmid deoxyribonucleic acid lipid nanoparticles for cell type-preferential transfection. ACS Nano. 2024;18(42):28735-28747. doi: 10.1021/acsnano.4c07615

 

  1. Rouco H, Diaz-Rodriguez P, Rama-Molinos S, Remuñán-López C, Landin M. Delimiting the knowledge space and the design space of nanostructured lipid carriers through Artificial Intelligence tools. Int J Pharm. 2018;553(1):522-530.doi: 10.1016/j.ijpharm.2018.10.058

 

  1. Petpiroon N, Netkueakul W, Sukrak K, et al. Development of lung tissue models and their applications. Life Sci. 2023;334:122208. doi: 10.1016/j.lfs.2023.122208

 

  1. Barbosa MAG, Xavier CPR, Pereira RF, Petrikaitė V, Vasconcelos MH. 3D cell culture models as recapitulators of the tumor microenvironment for the screening of anti-cancer drugs. Cancers (Basel). 2021;14(1):190. doi: 10.3390/cancers14010190

 

  1. Selo MA, Sake JA, Kim KJ, Ehrhardt C. In vitro and ex vivo models in inhalation biopharmaceutical research -advances, challenges and future perspectives. Adv Drug Deliv Rev. 2021;177:113862. doi: 10.1016/j.addr.2021.113862

 

  1. Stribbling SM, Beach C, Ryan AJ. Orthotopic and metastatic tumour models in preclinical cancer research. Pharmacol Ther. 2024;257:108631. doi: 10.1016/j.pharmthera.2024.108631

 

  1. He J, Zhang C, Ozkan A, et al. Patient-derived tumor models and their distinctive applications in personalized drug therapy. Mechanobiol Med. 2023;1(2):100014. doi: 10.1016/j.mbm.2023.100014

 

  1. Kersten K, de Visser KE, van Miltenburg MH, Jonkers J. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med. 2017;9(2):137-153. doi: 10.15252/emmm.201606857

 

  1. Zhang S, Xiao X, Yi Y, et al. Tumor initiation and early tumorigenesis: Molecular mechanisms and interventional targets. Signal Transduct Target Ther. 2024;9(1):149. doi: 10.1038/s41392-024-01848-7
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