Solid Lipid Nanoparticles: Fundamentals, Design and Applications
Chapter 10 - Solid Lipid Nanoparticles as Carrier for Ocular, Pulmonary, and Nasal Administration
Navyaja Kota, Jameel Ahmed S. Mulla, Pooja Vandan Pokar
Abstract:
Solid lipid nanoparticles (SLNs) have become a promising nanocarrier that can be used to deliver drugs in a non-invasive manner because of its biocompatibility, biodegradability, and the propensity to increase drug stability and bioavailability. Different modes of administration have different physiological barriers that tend to restrict effective delivery of the drug through the traditional dosage forms, including ocular, pulmonary, and nasal routes. The SLNs have immensely beneficial properties to address these hurdles, through enhancing drug absorption, increasing residence time at the site of action and being controlled or targeted to release drugs. This chapter gives an in depth review on the uses of solid lipid nanoparticles as carriers in administering drugs to the eye, lungs and nose. It explains the anatomical and physiological aspects of every route, formulation strategies, drug absorption mechanisms and treatment results obtained with the help of SLN-based systems. Also, recent research developments, safety issues, and regulatory outlooks are pointed out, as well as the contemporary challenges and opportunities.
Keywords: Solid lipid nanoparticles, SLNs, ocular drug delivery, pulmonary drug delivery, nasal drug delivery, non-invasive delivery, nanocarriers, controlled release, targeted drug delivery, pharmaceutical nanotechnology.
References:
[1] Kovacevic A, Savić S, Vuleta G, Müller RH, Keck CM. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): Effects on size, physical stability and particle matrix structure. International Journal of Pharmaceutics. 2011;406:163.
[2] Sandri G, Motta S, Bonferoni MC, Brocca P, Rossi S, Ferrari F, et al. Chitosan-coupled solid lipid nanoparticles: Tuning nanostructure and mucoadhesion. European Journal of Pharmaceutics and Biopharmaceutics. 2016;110:13.
[3] Kaushik A, Mazumder R, Padhi S, Mazumder A, Budhori R, Manorma, et al. Novel approaches in ocular drug delivery-a revolution. International Journal of Applied Pharmaceutics. 2022;1.
[4] Mali JD, Mulla JAS. Ocular drug delivery system: A review. World Journal of Drug Targeting. 2023;1(1):9.
[5] Mulla JAS, Khazi MIA, Khan AY, Gong YD, Khazi AM. Design, Characterization and In vitro Evaluation of Imidazo[2,1- b][1,3,4]thiadiazole Derivative Loaded Solid Lipid Nanoparticles. Drug Invention Today. 2012;4(8):420.
[6] Mulla J, Khazi I, Sharma NK, Hiremath S, Jamakandi V. Solid Lipid Nanoparticles: Methods of Preparation. Indian Journal of Novel Drug Delivery. 2011;3(3):170.
[7] Mulla J, Sharma NK, Khazi I. Solid Lipid Nanoparticles: Measures of Characterization. Indian Journal of Novel Drug Delivery. 2011;3(4):258.
[8] Bhatt S, Sharma JB, Singh M, Saini V. Solid lipid nanoparticles: a promising technology for delivery of poorly water-soluble drugs. ACTA Pharmaceutica Sciencia. 2018;56(3):27.
[9] Ahmed S, Amin MM, Sayed S. Ocular Drug Delivery: a Comprehensive Review. AAPS PharmSciTech. Springer Science; 2023;24(2).
[10] Sowmya C, Prakaash KKS, Ahmed HA. Solid lipid nanopartilces: Modern progress in nose-to-brain transduction. International Journal of Applied Pharmaceutics. 2023;20.
[11] Haripriyaa M, Suthindhiran K. Pharmacokinetics of nanoparticles: current knowledge, future directions and its implications in drug delivery. Future Journal of Pharmaceutical Sciences. 2023;9(1).
[12] Tyagi RK, Garg NK, Shukla R, Bisen PS. Role of Novel Drug Delivery Vehicles in Nanobiomedicine. IntechOpen eBooks. IntechOpen; 2019.
[13] Ramadon D. Solid Lipid Nanoparticles (SLN): Formulation and Fabrication. Pharmaceutical Sciences and Research. 2023;10(2).
[14] Mulla J, Khazi I. Influence of process variables on particle size of solid lipid nanoparticles. Indian Journal of Novel Drug Delivery. 2009;1(1):47.
[15] Mulla JAS, Hiremath SP, Sharma NK. Repaglinide Loaded Solid Lipid Nanoparticles: Design and Characterization. RGUHS J Pharm Sci. 2012;2(4):41.
[16] Bukke SPN, Venkatesh C, Rajanna SB, Saraswathi TS, Kusuma PK, Goruntla N, et al. Solid lipid nanocarriers for drug delivery: design innovations and characterization strategies—a comprehensive review. Discov Appl Sci. 2024;6:279.
[17] Mulla JAS, Shetty NS, Panchamukhi SI, Khazi IAM. Formulation, characterization and in vitro evaluation of novel thienopyrimidines and triazolothienopyrimidines loaded solid lipid nanoparticles. 2010; 1(1): 192-200.
[18] Mehnert W, Mäder K. Solid lipid nanoparticles: Production, characterization and applications. Advanced Drug Delivery Reviews. 2012;64:83-101.
[19] Mohammed HA, Khan R, 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. Nanotechnology Reviews. 2023;12(1).
[20] Mulla J, Khazi I, Jamakandi V. Solid lipid nanoparticles: Potential applications. Indian Journal of Novel Drug Delivery. 2010;2(3):82.
[21] Patole PJ, Mulla JAS. Liposomal In Situ Gel: A Novel Approach for the Treatment of Parkinson’s Disease via Intranasal Drug Delivery. Research Journal of Pharmaceutical Dosage Forms and Technology. 2025;17(1):53.
[22] González‐Fernández FM, Bianchera A, Gasco P, Nicoli S, Pescina S. Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation. Pharmaceutics [Internet]. Multidisciplinary Digital Publishing Institute; 2021;13(4):447.
[23] Chime AS. Lipid-based drug delivery systems (LDDS): Recent advances and applications of lipids in drug delivery. African Journal of Pharmacy and Pharmacology. 2013;7(48):3034.
[24] Dhiman N, Awasthi R, Sharma B, Kharkwal H, Kulkarni GT. Lipid Nanoparticles as Carriers for Bioactive Delivery. Frontiers in Chemistry. Frontiers Media; 2021;9.
[25] Nguyen T, Maeng H. Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery. Pharmaceutics [Internet]. Multidisciplinary Digital Publishing Institute; 2022;14(3):572.
[26] Khan S, Sharma A, Jain V. An Overview of Nanostructured Lipid Carriers and its Application in Drug Delivery through Different Routes. Advanced Pharmaceutical Bulletin [Internet]. Tabriz University of Medical Sciences; 2022;13(3):446.
[27] Shirke SN, Mulla JAS. Intranasal Nanoemulsion for Brain Targeting: A Review. Indian Journal of Novel Drug Delivery. 2023;15(1):1.
[28] Mulla JA, Suresh S, Khazi IA. Formulation, Characterization and in vitro Evaluation of Methotrexate Solid Lipid Nanoparticles. Research Journal of Pharmacy and Technology. 2009;2(4):685.
[29] Gaetano FD, Celesti C, Paladini G, Venuti V, Cristiano MC, Paolino D, et al. Solid Lipid Nanoparticles Containing Morin: Preparation, Characterization, and Ex Vivo Permeation Studies. Pharmaceutics. 2023;15(6):1605.
[30] Mulla J, Jokar SP, Jamakandi V. Preparation, Characterization and In vitro Evaluation of 5-Fluorouracil loaded Solid Lipid Nanoparticles. Indian Journal of Novel Drug Delivery. 2010;2(1):11.
[31] Ashique S, Mishra N, Mohanto S, Gowda BHJ, Kumar S, Raikar AS, et al. Overview of processed excipients in ocular drug delivery: Opportunities so far and bottlenecks. Heliyon. 2023;10(1).
[32] Razavi MS, Ebrahimnejad P, Fatahi Y, D’Emanuele A, Dinarvand R. Recent Developments of Nanostructures for the Ocular Delivery of Natural Compounds. Frontiers in Chemistry. Frontiers Media; 2022;10.
[33] Atabakhshi‐Kashi M, Geranpayehvaghei M, Wang Y, Akhbariyoon H, Taleb M, Zhang Y, et al. Recent Advances of Nanocarriers for Effective Delivery of Therapeutic Peptides. Precision Nanomedicine. 2020;3(2).
[34] Shewale SS, Mulla JAS. Non-Ionic Surfactant Vesicle (Niosome): A Novel Drug Delivery System. Indian Journal of Novel Drug Delivery. 2022;14(3):129.
[35] Gugleva V, Andonova V. Recent Progress of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Ocular Drug Delivery Platforms. Pharmaceuticals. Multidisciplinary Digital Publishing Institute; 2023;16(3):474.
[36] Geszke-Moritz M, Moritz M. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies. Materials Science and Engineering C. Elsevier BV; 2016;68:982.
[37] Duan Y, Dhar A, Patel CN, Khimani M, Neogi S, Sharma P, et al. A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems. RSC Advances. Royal Society of Chemistry; 2020;10(45):26777.
[38] Naseri N, Valizadeh H, Zakeri‐Milani P. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application. Advanced Pharmaceutical Bulletin. Tabriz University of Medical Sciences; 2015;5(3):305.
[39] Kumari ChS, Rao NS, Begham SkA, Babu SS, Rao G, Rao KV. Formulation techniques of lipid based nanoparticles: sln/nlcs, its evaluation and applications. International Journal of Research in Pharmacy and Chemistry. 2020;10(1).
[40] Begum MS, Shaik NB. Solid Lipid Nanoparticles: A Review. Indo Global Journal of Pharmaceutical Sciences. 2021;11(2):100.
[41] Joshi RKH. Solid Lipid Nanoparticle: A Review. IOSR Journal of Pharmacy (IOSRPHR). 2012;2(6):34.
[42] M NK, S S, P SR, Narayanasamy D. The Science of Solid Lipid Nanoparticles: From Fundamentals to Applications. Cureus. 2024;16(9):e68807.
[43] Luo MX, Hua S, Shang QY. Application of nanotechnology in drug delivery systems for respiratory diseases (Review). Molecular Medicine Reports. Spandidos Publishing; 2021;23(5).
[44] Iyer R, Hsia CCW, Nguyen KT. Nano-Therapeutics for the Lung: State-of-the-Art and Future Perspectives. Current Pharmaceutical Design. Bentham Science Publishers; 2015;21(36):5233.
[45] Alexescu T, Țărmure S, Negrean V, Cosnarovici MM, Ruta VM, Popovici I, et al. Nanoparticles in the treatment of chronic lung diseases. Journal of Mind and Medical Sciences. 2019;6(2):224.
[46] Peng S, Wang W, Zhang R, Wu C, Pan X, Huang Z. Nano-Formulations for Pulmonary Delivery: Past, Present, and Future Perspectives. Pharmaceutics. 2024;16(2):161.
[47] Ezzati A, Valizadeh H, Hamishehkar H. Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs. Advanced Pharmaceutical Bulletin. Tabriz University of Medical Sciences; 2015;5(2):151.
[48] Mehrdadi S. Solid Lipid Nanoparticles: a promising drug delivery system and their potential for peptide and protein therapeutics. In: IntechOpen eBooks. IntechOpen; 2024.
[49] Cunha S, Amaral MH, Lobo JMS, Silva AC. Lipid Nanoparticles for Nasal/Intranasal Drug Delivery. Critical Reviews in Therapeutic Drug Carrier Systems. Begell House; 2017;34(3):257.
[50] Agosti E, Zeppieri M, Antonietti S, Battaglia L, Ius T, Gagliano C, et al. Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders. Pharmaceutics [Internet]. Multidisciplinary Digital Publishing Institute; 2024 Feb 27 [cited 2025 Nov];16(3):329.Availablefrom: https://doi.org/10.3390/pharmaceutics16030329
[51] Garud A, Singh D, Garud N. Solid Lipid Nanoparticles (SLN): Method, Characterization and Applications. International Current Pharmaceutical Journal. 2012;1(11):384.
[52] Correia A de A, Monteiro AR, Silva RBMD, Moreira JN, Lobo JMS, Silva AC. Lipid nanoparticles strategies to modify pharmacokinetics of central nervous system targeting drugs: Crossing or circumventing the blood–brain barrier (BBB) to manage neurological disorders. Advanced Drug Delivery Reviews. Elsevier BV; 2022;189:114485.
[53] Raj RK, Kolay A, Havelikar U. A review on solid lipid nanoparticles. International Journal of Current Pharmaceutical Research. 2023;10.
[54] Satapathy MK, Yen T, Jan J, Tang RD, Wang J, Taliyan R, et al. Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB. Pharmaceutics. Multidisciplinary Digital Publishing Institute; 2021;13(8):1183.
[55] Tapeinos C, Battaglini M, Ciofani G. Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. Journal of Controlled Release. Elsevier BV; 2017;264:306.
[56] Montoto SS, Muraca G, Ruiz ME. Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects. Frontiers in Molecular Biosciences. Frontiers Media; 2020;7.
[57] Mujawar N, Mulla JAS. Lipid-Polymer Hybrid Nanoparticles in Cancer Therapy: A Promising Nanotechnology-Based Drug Delivery System. International Journal of Pharmaceutical Sciences and Drug Research. 2025;17(4):371.
[58] Kumar K, Singh RK, Tyagi P, Gore D. Assessment of Toxicity and Safety Profiles of Nanoparticles. Letters in Applied NanoBioScience. 2020;10(1):1877.
[59] Doktorovová S, Kovacevic A, García ML, Souto EB. Preclinical safety of solid lipid nanoparticles and nanostructured lipid carriers: Current evidence from in vitro and in vivo evaluation. European Journal of Pharmaceutics and Biopharmaceutics. 2016;108:235.