Solid Lipid Nanoparticles: Fundamentals, Design and Applications
Chapter 8 - Topical and Transdermal Applications of Solid Lipid Nanoparticles
Nigar Kadar Mujawar, Nupoor Sunil Erram, Jameel Ahmed S. Mulla
Abstract:
Solid lipid nanoparticles (SLN) are emerging as efficient as possible nanocarrierswith special physicochemical characteristics for topical, in addition to transdermal, medication delivery, biocompatibility, as well as being able to boost skin penetration. SLNs are made of solid lipids stabilised by surfactants and stay solid at both atmospheric and human body temperatures, giving controlled release of medications, improved drug stability, and protection of labile compounds. This chapter presents a comprehensive overview of the fundamentals, design principles, and therapeutic applications of SLNs in dermal drug delivery systems. This chapter begins with the basic principles and historical development of SLNs, discussing their composition, mechanisms of drug encapsulation, and comparison with other colloidal carriers like liposomes and nanostructured lipid carriers (NLCs). There is a thorough examination of important physicochemical properties, including stability, the loading of drugs, zeta potential, along with size of particles. Various formulation strategies and production methods, including high-pressure homogenization, microemulsion techniques, and solvent evaporation, are reviewed, alongside optimisation tools like Quality by Design (QbD). Topical applications of SLNs in dermatology and cosmetics highlight their benefits in treating conditions such as acne, psoriasis, and skin ageing, while transdermal applications focus on systemic delivery of drugs like Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and hormones. The review also discusses evaluation methodologies, regulatory challenges, and potential toxicity concerns. Recent innovations, including stimuli-responsive and microneedle-assisted SLNs, are highlighted to showcase future directions. Overall, SLNs represent a versatile platform for safe and effective dermal drug delivery, offering promising potential in both clinical and cosmetic fields.
Keywords: Biocompatibility, Controlled Drug Release, Dermatological Applications, Drug Encapsulation, Formulation Techniques, Microneedle Assisted Delivery, Physicochemical Properties, Skin Permeation Enhancement, Stimuli-Responsive Nanocarriers, Topical Drug Delivery, Transdermal Delivery.
References:
[1] Jasti BR, Abraham W, Ghosh TK. Transdermal and Topical drug delivery systems. In Theory and practice of contemporary pharmaceutics 2021 Feb 25 (pp. 423-454). CRC Press.
[2] Uchechi O, Ogbonna JD, Attama AA. Nanoparticles for dermal and transdermal drug delivery. Application of nanotechnology in drug delivery. 2014 Jul 25;4:193-227.
[3] Akombaetwa N, Ilangala AB, Thom L, Memvanga PB, Witika BA, Buya AB. Current advances in lipid nanosystems intended for topical and transdermal drug delivery applications. Pharmaceutics. 2023 Feb 15;15(2):656.
[4] Tapfumaneyi P, Imran M, Mohammed Y, Roberts MS. Recent advances and future prospective of topical and transdermal delivery systems. Frontiers in Drug Delivery. 2022 Sep 5;2:957732.
[5] Rehman K, Zulfakar MH. Recent advances in gel technologies for topical and transdermal drug delivery. Drug development and industrial pharmacy. 2014 Apr 1;40(4):433-40.
[6] Abla MJ, Singh ND, Banga AK. Role of nanotechnology in skin delivery of drugs. In Percutaneous penetration enhancers chemical methods in penetration enhancement: nanocarriers 2016 Jan 5 (pp. 1-13). Berlin, Heidelberg: Springer Berlin Heidelberg.
[7] Zhou X, Hao Y, Yuan L, Pradhan S, Shrestha K, Pradhan O, Liu H, Li W. Nano-formulations for transdermal drug delivery: A review. Chinese Chemical Letters. 2018 Dec 1;29(12):1713-24.
[8] Alsaad AA, Hussien AA, Gareeb MM. Solid lipid nanoparticles (SLN) as a novel drug delivery system: A theoretical review. Syst. Rev. Pharm. 2020 May 1;11(5):259-73.
[9] Lingayat VJ, Zarekar NS, Shendge RS. Solid lipid nanoparticles: a review. Nanosci. Nanotechnol. Res. 2017 Apr;4(2):67-72.
[10] Viegas C, Patrício AB, Prata JM, Nadhman A, Chintamaneni PK, Fonte P. Solid lipid nanoparticles vs. nanostructured lipid carriers: a comparative review. Pharmaceutics. 2023 May 25;15(6):1593.
[11] Kumar R, Dkhar DS, Kumari R, Mahapatra S, Dubey VK, Chandra P. Lipid based nanocarriers: Production techniques, concepts, and commercialization aspect. Journal of Drug Delivery Science and Technology. 2022 Aug 1;74:103526.
[12] Naseri N, Valizadeh H, Zakeri-Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Advanced pharmaceutical bulletin. 2015 Sep 19;5(3):305.
[13] Gordillo-Galeano A, Mora-Huertas CE. Solid lipid nanoparticles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. European Journal of Pharmaceutics and Biopharmaceutics. 2018 Dec 1;133:285-308.
[14] Kullavadee KO, Uracha R, Smith SM. Effect of surfactant on characteristics of solid lipid nanoparticles (SLN). Advanced Materials Research. 2012 Jan 30;364:313-6.
[15] Bunjes H, Koch MH, Westesen K. Influence of emulsifiers on the crystallization of solid lipid nanoparticles. Journal of pharmaceutical sciences. 2003 Jul 1;92(7):1509-20.
[16] Jasim AM, Jawad MJ. Pharmaceutical Applications of Vitamin E TPGS. IntechOpen; 2021 Aug 30.
[17] Subroto E, Andoyo R, Indiarto R. Solid lipid nanoparticles: Review of the current research on encapsulation and delivery systems for active and antioxidant compounds. Antioxidants. 2023 Mar;12(3):633.
[18] Parhi R, Suresh P. Production of solid lipid nanoparticles-drug loading and release mechanism. J Chem Pharm Res. 2010;2(1):211-7.
[19] Zhang J, Purdon CH, Smith EW. Solid lipid nanoparticles for topical drug delivery. American Journal of Drug Delivery. 2006 Dec;4:215-20.
[20] Son GH, Lee BJ, Cho CW. Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles. Journal of Pharmaceutical Investigation. 2017 Jul;47:287-96.
[21] Parhi R, Suresh P. Production of solid lipid nanoparticles-drug loading and release mechanism. J Chem Pharm Res. 2010;2(1):211-7.
[22] Göppert TM, Müller RH. Adsorption kinetics of plasma proteins on solid lipid nanoparticles for drug targeting. International journal of pharmaceutics. 2005 Sep 30;302(1-2):172-86.
[23] Almeida AJ, Souto E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Advanced drug delivery reviews. 2007 Jul 10;59(6):478-90.
[24] Hussein HA, Khaphi FL, Sivaramakrishnan R, Poornima S, Abdullah MA. Recent developments in sustained-release and targeted drug delivery applications of solid lipid nanoparticles. Journal of Microencapsulation. 2025 Apr 29:1-31.
[25] Priya S, Desai VM, Singhvi G. Surface modification of lipid-based nanocarriers: a potential approach to enhance targeted drug delivery. ACS omega. 2022 Dec 20;8(1):74-86
[26] Mohammed HA, Khan RA, Singh V, Yusuf M, Akhtar N, Sulaiman GM, Albukhaty S, Abdellatif AA, Khan M, Mohammed SA, Al-Subaiyel AM. 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 Feb 18;12(1):20220517.
[27] Pande S. Liposomes for drug delivery: review of vesicular composition, factors affecting drug release and drug loading in liposomes. Artificial Cells, Nanomedicine, and Biotechnology. 2023 Dec 31;51(1):428-40.
[28] de Barros DP, Reed P, Alves M, Santos R, Oliva A. Biocompatibility and antimicrobial activity of nanostructured lipid carriers for topical applications are affected by type of oils used in their composition. Pharmaceutics. 2021 Nov 17;13(11):1950.
[29] Dymek M, Sikora E. Liposomes as biocompatible and smart delivery systems–the current state. Advances in colloid and interface science. 2022 Nov 1;309:102757.
[30] Danaei MR, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018 May 18;10(2):57.
[31] Westesen K, Bunjes H, Koch MH. Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. Journal of controlled release. 1997 Oct 13;48(2-3):223-36.
[32] Hou D, Xie C, Huang K, Zhu C. The production and characteristics of solid lipid nanoparticles (SLNs). Biomaterials. 2003 May 1;24(10):1781-5.
[33] Freitas C, Müller RH. Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase. European journal of pharmaceutics and biopharmaceutics. 1999 Mar 1;47(2):125-32.
[34] Makoni PA, Wa Kasongo K, Walker RB. Short term stability testing of efavirenz-loaded solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Pharmaceutics. 2019 Aug 8;11(8):397.
[35] Souto EB, Baldim I, Oliveira WP, Rao R, Yadav N, Gama FM, Mahant S. SLN and NLC for topical, dermal, and transdermal drug delivery. Expert opinion on drug delivery. 2020 Mar 3;17(3):357-77.
[36] 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. Nanotechnology Reviews. 2022 Apr 22;11(1):1744-77.
[37] Yadav V, AlokMahor S, Alok S, AmitaVerma A, Kumar N, Kumar S. Solid lipid nanoparticles (sln): formulation by high pressure homogenization. World J Pharm Pharm Sci. 2014 Sep 12;3(11):1200-3.
[38] Vinchhi P, Patel JK, Patel MM. High-pressure homogenization techniques for nanoparticles. InEmerging Technologies for Nanoparticle Manufacturing 2021 Jun 24 (pp. 263-285). Cham: Springer International Publishing.
[39] Shah RM, Malherbe F, Eldridge D, Palombo EA, Harding IH. Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by a novel microemulsion technique. Journal of colloid and interface science. 2014 Aug 15;428:286-94.
[40] Marquez R, Ontiveros JF, Barrios N, Tolosa L, Palazzo G, Nardello‐Rataj V, Salager JL. Advantages and limitations of different methods to determine the optimum formulation in surfactant–oil–water systems: a review. Journal of Surfactants and Detergents. 2024 Jan;27(1):5-36.
[41] Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification–diffusion technique. International journal of pharmaceutics. 2003 May 12;257(1-2):153-60.
[42] Khairnar SV, Pagare P, Thakre A, Nambiar AR, Junnuthula V, Abraham MC, Kolimi P, Nyavanandi D, Dyawanapelly S. Review on the scale-up methods for the preparation of solid lipid nanoparticles.Pharmaceutics. 2022 Sep 6;14(9):1886.
[43] Vyas SP, Rai S, Paliwal R, Gupta PN, Khatri K, Goyal AK, Vaidya B. Solid lipid nanoparticles (SLNs) as a rising tool in drug delivery science: one step up in nanotechnology. Current Nanoscience. 2008 Feb 1;4(1):30-44.
[44] Luiz MT, Viegas JS, Abriata JP, Viegas F, de Carvalho Vicentini FT, Bentley MV, Chorilli M, Marchetti JM, Tapia-Blacido DR. Design of experiments (DoE) to develop and to optimize nanoparticles as drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics. 2021 Aug 1;165:127-48.
[45] Rampado R, Peer D. Design of experiments in the optimization of nanoparticle-based drug delivery systems. Journal of controlled release. 2023 Jun 1;358:398-419.
[46] zur Mühlen A, Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery–drug release and release mechanism. European journal of pharmaceutics and biopharmaceutics. 1998 Mar 1;45(2):149-55.
[47] Sarker DK. Engineering of nanoemulsions for drug delivery. Current drug delivery. 2005 Oct 1;2(4):297-310.
[48] Ahmad J. Lipid nanoparticles based cosmetics with potential application in alleviating skin disorders. Cosmetics. 2021 Sep 7;8(3):84.
[49] Souto EB, Müller RH. Cosmetic features and applications of lipid nanoparticles (SLN®, NLC®). International journal of cosmetic science. 2008 Jun;30(3):157-65.
[50] Trombino S, Cassano R. Solid lipid nanoparticles for topical drug delivery. InDrug Delivery Approaches and Nanosystems, Volume 2 2017 Nov 15 (pp. 317-332). Apple Academic Press.
[51] Yu YQ, Yang X, Wu XF, Fan YB. Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: novel strategies for effective transdermal applications. Frontiers in bioengineering and biotechnology. 2021 Mar 29;9:646554.
[52] Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages. Research in pharmaceutical sciences. 2018 Aug 1;13(4):288-303.
[53] Jijie R, Barras A, Boukherroub R, Szunerits S. Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures. Journal of Materials Chemistry B. 2017;5(44):8653-75.
[54] Moghimipour E, Khazali M, MakhmalZadeh BS, Abedini Baghbadorani M, Zangeneh A, Sohrabi S, Nejaddehbashi F, Hajipour F, Handali S. Development of propranolol loaded SLN for transdermal delivery: in-vitro characterization and skin deposition studies. Therapeutic Delivery. 2025 Jan 30:1-1.
[55] Nunes D, Loureiro JA, Pereira MC. Drug delivery systems as a strategy to improve the efficacy of FDA-approved Alzheimer’s drugs. Pharmaceutics. 2022 Oct 26;14(11):2296.
[56] Liu D, Ge Y, Tang Y, Yuan Y, Zhang Q, Li R, Xu Q. Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation, characterization and in vitro studies. Journal of microencapsulation. 2010 Dec 1;27(8):726-34.
[57] Aydin BS, Sagiroglu AA, Ozturk Civelek D, Gokce M, Bahadori F. Development of curcumin and turmerone loaded solid lipid nanoparticle for topical delivery: Optimization, characterization and skin irritation evaluation with 3D tissue model. International Journal of Nanomedicine. 2024 Dec 31:1951-66.
[58] Chauhan MK, Sharma PK. Optimization and characterization of rivastigmine nanolipid carrier loaded transdermal patches for the treatment of dementia. Chemistry and physics of lipids. 2019 Nov 1;224:104794 2022 Oct 26;14(11):2296.
[59] Chauhan MK, Sharma PK. Optimization and characterization of rivastigmine nanolipid carrier loaded transdermal patches for the treatment of dementia. Chemistry and physics of lipids. 2019 Nov 1;224:104794
[60] Garud A, Singh D, Garud N. Solid lipid nanoparticles (SLN): method, characterization and applications. International Current Pharmaceutical Journal. 2012 Oct 3;1(11):384-93.
[61] Qi J, Lu Y, Wu W. Absorption, disposition and pharmacokinetics of solid lipid nanoparticles. Current Drug Metabolism. 2012 May 1;13(4):418-28.
[62] Hernández-Esquivel RA, Navarro-Tovar G, Zárate-Hernández E, Aguirre-Bañuelos P. Solid lipid nanoparticles (SLN). InNanocomposite materials for biomedical and energy storage applications 2022 Nov 2. IntechOpen.
[63] Andonova V, Peneva P. Characterization methods for solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Current pharmaceutical design. 2017 Dec 1;23(43):6630-42.
[64] Guilherme VA, Ribeiro LN, Tofoli GR, Franz-Montan M, de Paula E, de Jesus MB. Current challenges and future of lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye. Current pharmaceutical design. 2017 Dec 1;23(43):6659-75.
[65] Mehta M, Bui TA, Yang X, Aksoy Y, Goldys EM, Deng W. Lipid-based nanoparticles for drug/gene delivery: an overview of the production techniques and difficulties encountered in their industrial development. ACS Materials Au. 2023 Aug 21;3(6):600-19.
[66] Souto EB, Blanco-Llamero C, Krambeck K, Kiran NS, Yashaswini C, Postwala H, Severino P, Priefer R, Prajapati BG, Maheshwari R. Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives. Acta biomaterialia. 2024 Apr 10.
[67] Shahi F, Afshar H, Dawi EA, Khonakdar HA. Smart Microneedles in Biomedical Engineering: Harnessing Stimuli‐Responsive Polymers for Novel Applications. Polymers for Advanced Technologies. 2024 Dec;35(12):e70020.
[68] Mahammed N. Stimuli-responsive nanomaterials: Innovations in on-demand drug release systems. Asian Journal of Pharmaceutics (AJP). 2025 Mar 15;19(01).
[69] Marwah H, Dewangan HK. Advancements in solid lipid nanoparticles and nanostructured lipid carriers for breast cancer therapy. Current pharmaceutical design. 2024 Oct;30(37):2922-36.