Lipid-Based Nanocarriers for Oral Drug Delivery: Advances, Challenges, and Clinical Prospects
Abstract
Lipid-based nanocarriers have gained significant attention in oral drug delivery due to their ability to enhance solubility, bioavailability, and therapeutic efficacy of poorly water-soluble drugs. Among these, Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) are widely explored for their controlled drug release, stability, and improved absorption via mechanisms such as lymphatic transport and mucus penetration. Recent advancements, including surface modifications (PEGylation), functionalization with bioadhesive ligands, and pH-sensitive lipid formulations, have further improved their performance. However, challenges related to stability, large-scale manufacturing, and regulatory approval remain critical barriers to clinical translation. Several lipid-based formulations have already entered clinical trials, demonstrating potential in treating cancer, diabetes, and infectious diseases. Future research should focus on novel lipid excipients, personalized drug formulations, and advanced manufacturing techniques to facilitate the commercialization of these nanocarriers. This review highlights the latest advancements, challenges, and future prospects of lipid-based nanocarriers for efficient and patient-friendly oral drug delivery systems.
References
Mathias NR, Hussain MA. Non-invasive systemic drug delivery: developability considerations for alternate routes of administration. J Pharm Sci. 2010;99(1):1–20.
2. Lou J, Duan H, Qin Q, Teng Z, Gan F, Zhou X, et al. Advances in oral drug delivery systems: Challenges and opportunities. Pharmaceutics. 2023;15(2):484.
3. Papich MG, Martinez MN. Applying biopharmaceutical classification system (BCS) criteria to predict oral absorption of drugs in dogs: challenges and pitfalls. AAPS J. 2015;17:948–64.
4. Mishra DK, Shandilya R, Mishra PK. Lipid based nanocarriers: a translational perspective. Nanomedicine Nanotechnology, Biol Med. 2018;14(7):2023–50.
5. 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.
6. Talegaonkar S, Bhattacharyya A. Potential of lipid nanoparticles (SLNs and NLCs) in enhancing oral bioavailability of drugs with poor intestinal permeability. Aaps Pharmscitech. 2019;20(3):121.
7. Lim SB, Banerjee A, Önyüksel H. Improvement of drug safety by the use of lipid-based nanocarriers. J Control release. 2012;163(1):34–45.
8. Satapathy MK, Yen TL, Jan JS, Tang RD, Wang JY, Taliyan R, et al. Solid lipid nanoparticles (SLNs): an advanced drug delivery system targeting brain through BBB. Pharmaceutics. 2021;13(8):1183.
9. Kesharwani R, Jaiswal P, Patel DK, Yadav PK. Lipid-based drug delivery system (LBDDS): An emerging paradigm to enhance oral bioavailability of poorly soluble drugs. Biomed Mater Devices. 2023;1(2):648–63.
10. Han H, Li S, Xu M, Zhong Y, Fan W, Xu J, et al. Polymer-and lipid-based nanocarriers for ocular drug delivery: current status and future perspectives. Adv Drug Deliv Rev. 2023;196:114770.
11. Kumar R, Dkhar DS, Kumari R, Mahapatra S, Dubey VK, Chandra P. Lipid based nanocarriers: Production techniques, concepts, and commercialization aspect. J Drug Deliv Sci Technol. 2022;74:103526.
12. Svilenov H, Tzachev C. Solid lipid nanoparticles—a promising drug delivery system. Nanomedicine. 2014;8:188–237.
13. Alsaad AAA, Hussien AA, Gareeb MM. Solid lipid nanoparticles (SLN) as a novel drug delivery system: A theoretical review. Syst Rev Pharm. 2020;11(5):259–73.
14. Kathe N, Henriksen B, Chauhan H. Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations. Drug Dev Ind Pharm. 2014;40(12):1565–75.
15. Tamjidi F, Shahedi M, Varshosaz J, Nasirpour A. Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules. Innov Food Sci Emerg Technol. 2013;19:29–43.
16. Kalepu S, Manthina M, Padavala V. Oral lipid-based drug delivery systems–an overview. Acta Pharm Sin B. 2013;3(6):361–72.
17. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29(3–4):278–87.
18. Vishwakarma N, Jain A, Sharma R, Mody N, Vyas S, Vyas SP. Lipid-based nanocarriers for lymphatic transportation. AAPS PharmSciTech. 2019;20(2):83.
19. Alp G, Aydogan N. Lipid-based mucus penetrating nanoparticles and their biophysical interactions with pulmonary mucus layer. Eur J Pharm Biopharm. 2020;149:45–57.
20. Esfanjani AF, Assadpour E, Jafari SM. Improving the bioavailability of phenolic compounds by loading them within lipid-based nanocarriers. Trends Food Sci Technol. 2018;76:56–66.
21. De Leo V, Milano F, Agostiano A, Catucci L. Recent advancements in polymer/liposome assembly for drug delivery: from surface modifications to hybrid vesicles. Polymers (Basel). 2021;13(7):1027.
22. Rao S, Prestidge CA. Polymer-lipid hybrid systems: merging the benefits of polymeric and lipid-based nanocarriers to improve oral drug delivery. Expert Opin Drug Deliv. 2016;13(5):691–707.
23. El Moukhtari SH, Rodriguez-Nogales C, Blanco-Prieto MJ. Oral lipid nanomedicines: current status and future perspectives in cancer treatment. Adv Drug Deliv Rev. 2021;173:238–51.
24. Plaza-Oliver M, Santander-Ortega MJ, Lozano MV. Current approaches in lipid-based nanocarriers for oral drug delivery. Drug Deliv Transl Res. 2021;11:471–97.
25. Xu Y, Fourniols T, Labrak Y, Préat V, Beloqui A, des Rieux A. Surface modification of lipid-based nanoparticles. ACS Nano. 2022;16(5):7168–96.
26. Liu L, Yao W, Rao Y, Lu X, Gao J. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms. Drug Deliv. 2017;24(1):569–81.
27. Karanth H, Murthy RSR. pH‐Sensitive liposomes‐principle and application in cancer therapy. J Pharm Pharmacol. 2007;59(4):469–83.
28. Yi Xue H, Guo P, Wen WC, Lun Wong H. Lipid-based nanocarriers for RNA delivery. Curr Pharm Des. 2015;21(22):3140–7.
29. Gomes-da-Silva LC, Fonseca NA, Moura V, Pedroso de Lima MC, Simões S, Moreira JN. Lipid-based nanoparticles for siRNA delivery in cancer therapy: paradigms and challenges. Acc Chem Res. 2012;45(7):1163–71.
30. Mohammed HA, Khan RA, Singh V, Yusuf M, Akhtar N, Sulaiman GM, et al. Solid lipid nanoparticles for targeted natural and synthetic drugs delivery in high-incidence cancers, and other diseases: Roles of preparation methods, lipid composition, transitional stability, and release profiles in nanocarriers’ development. Nanotechnol Rev. 2023;12(1):20220517.
31. Musakhanian J, Rodier JD, Dave M. Oxidative stability in lipid formulations: a review of the mechanisms, drivers, and inhibitors of oxidation. AAPS PharmSciTech. 2022;23(5):151.
32. Ragelle H, Danhier F, Préat V, Langer R, Anderson DG. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Expert Opin Drug Deliv. 2017;14(7):851–64.
33. Savla R, Browne J, Plassat V, Wasan KM, Wasan EK. Review and analysis of FDA approved drugs using lipid-based formulations. Drug Dev Ind Pharm. 2017;43(11):1743–58.
34. Jain S, Kambam S, Thanki K, Jain AK. Cyclosporine A loaded self-nanoemulsifying drug delivery system (SNEDDS): implication of a functional excipient based co-encapsulation strategy on oral bioavailability and nephrotoxicity. RSC Adv. 2015;5(61):49633–42.
35. Ansari H, Singh P. Lipid based anti-retroviral nanocarriers: a review of current literature and ongoing studies. Drug Deliv Lett. 2017;7(2):71–82.
36. Tziomalos K, Athyros VG. Fenofibrate: a novel formulation (TriglideTM) in the treatment of lipid disorders: a review. Int J Nanomedicine. 2006;1(2):129–47.
37. Katiyar SS, Patil R, Ghadi R, Kuche K, Kushwah V, Dora CP, et al. Lipid-and TPGS-based core–shell-type nanocapsules endowed with high paclitaxel loading and enhanced anticancer potential. AAPS PharmSciTech. 2022;23(7):238.
38. Grabska-Kobyłecka I, Szpakowski P, Król A, Książek-Winiarek D, Kobyłecki A, Głąbiński A, et al. Polyphenols and their impact on the prevention of neurodegenerative diseases and development. Nutrients. 2023;15(15):3454.
39. Walvekar P, Gannimani R, Govender T. Combination drug therapy via nanocarriers against infectious diseases. Eur J Pharm Sci. 2019;127:121–41.
40. Chen ML. Lipid excipients and delivery systems for pharmaceutical development: a regulatory perspective. Adv Drug Deliv Rev. 2008;60(6):768–77.
41. Abdelhamid M, Corzo C, Urich JAA, Slama E, Fröhlich E, Lochmann D, et al. Personalization of lipid-based oral dosage forms via filament-based 3D-printing. Appl Mater Today. 2024;40:102399.
42. Zhong Y, Wang B, Lv W, Wu Y, Lv Y, Sheng S. Recent research and applications in lipid-based food and lipid-incorporated bioink for 3D printing. Food Chem. 2024;140294.
43. Osouli-Bostanabad K, Puliga S, Serrano DR, Bucchi A, Halbert G, Lalatsa A. Microfluidic manufacture of lipid-based nanomedicines. Pharmaceutics. 2022;14(9):1940.
44. Durán-Lobato M, Enguix-González A, Fernández-Arévalo M, Martín-Banderas L. Statistical analysis of solid lipid nanoparticles produced by high-pressure homogenization: a practical prediction approach. J nanoparticle Res. 2013;15:1–14.
45. Berraquero-García C, Pérez-Gálvez R, Espejo-Carpio FJ, Guadix A, Guadix EM, García-Moreno PJ. Encapsulation of bioactive peptides by spray-drying and electrospraying. Foods. 2023;12(10):2005.
46. Martínez-Muñoz OI, Mora-Huertas CE. Nanoprecipitation technology to prepare carrier systems of interest in pharmaceutics: An overview of patenting. Int J Pharm. 2022;614:121440.
