Abstract
Nanotechnology is expected to revolutionize existing drug delivery. Many nanostructured systems have been employed for drug delivery and yielded some promising results. Solid lipid nanoparticles (SLN) have been looked at as a potential drug carrier system since last two decades. SLN do not show biotoxicity as they are prepared from physiological lipids. SLN are especially useful in drug delivery as they can enhance the absorption of drugs and improves the bioavailability of both hydrophilic and lipophilic drugs. This paper presents an overview about the various classes of SLN, comparison with available drug carrier systems, different ways of production, in vivo fate and biodistribution and various applications of SLN. Besides, aspects of stability, hurdles and strategies for SLN manufacturing with potential of clinical translation are also discussed.
Similar content being viewed by others
Abbreviations
- NDDS:
-
Novel drug delivery system
- SLN:
-
Solid lipid nanoparticles
- DDS:
-
Drug delivery system
- NLC:
-
Nanostructured lipid carriers
- SCF:
-
Supercritical fluid technology
- SFEE:
-
Supercritical fluid extraction of emulsions
- GAMA:
-
Gas-assisted melting atomisation
- O/W:
-
Oil-in-water
- CM:
-
Mixing chamber
- TEM:
-
Transmission electron microscopy
- SEM:
-
Scanning electron microscopy
- PCM:
-
Phase contrast optical microscopy
- AFM:
-
Atomic force microscopy
- PCS:
-
Photon correlation spectroscopy
- SAX:
-
Synchrotron radiation X-ray
- GPC:
-
Gel permeation chromatography
- SWCNT:
-
Single-walled carbon nanotubes
- TMS:
-
Thermosensitive magneto liposomes
- MTX:
-
Methotrexate
- MBC:
-
Metastatic breast cancer
- PNET:
-
Phase nanoparticle engineering technology
- cSLN:
-
Cationic solid lipid nanoparticles
- PTX:
-
Paclitaxel
- ADA:
-
Adenosine deaminase
- DNA:
-
Deoxyribonucleic acid
References
Muhlen A, Schwarz C, Mehnert W. Solid lipid nanoparticles for controlled drug delivery—drug release and release mechanism. Eur J Pharm Biopharm. 1998;45:149–55.
Muhlen A, Schwarz C, Wolfgang M. Solid Lipid nanoparticles for controlled drug delivery—drug release and release mechanism. Eur J Pharm Biopharm. 1998;45(2):149–55.
Muhlen Z, Mehnert W. Drug release and release mechanism of prednisolone loaded solid lipid nanoparticles. Pharmazie. 1998;53:552–5.
Almeida A, Souto E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv Drug Del Rev. 2007;59(6):478–90.
Andrea M, Calderoni S, Gian P, Lorenzo P, Maria R, Alessandro M. Solid lipid nanoparticles for brain tumors therapy: state of the art and novel challenges. Progress in Brain Res. 2009;180:193–223.
Diepold R, Kreuter J, Guggenbuhl P. Distribution of poly-hexyl-2-cyano-[3–14C] acrylate nanoparticles in healthy and chronically inflamed rabbit eyes. Int J Pharm. 1989;54:149–53.
Chakraborty S, Shukla D, Mishra B, Singh S. Lipid—an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm. 2009;73(1):1–15.
Wolfgang M, Mader K. Solid lipid nanoparticles production, characterization and applications. Adv Drug Del Rev. 2001;47(2–3):165–96.
Marcelo B, Carmen V, Eneida P, Dick H. Solid lipid nanoparticles for gene delivery into prostate cancer cells. Drug Discov Today. 2010;15(23–24):1110.
Fang J, Chia L, Chi L. Lipid nanoparticles as vehicles for topical psoralen delivery solid lipid nanoparticles versus nanostructured lipid carriers. Eur J Pharm Biopharm. 2008;70(2):633–40.
Mudshinge R, Deore A, Patil S, Bhalgat C. Nanoparticles emerging carriers for drug delivery. Saudi Pharm J. 2011;19(3):129–41.
Runge S, Mechnert W, Muller R. Solid lipid nanoparticles, a novel formulation for the oral administration of drugs. Eur J Pharm Sci. 1996;4(1):S132.
Garti N. Effects of surfactants on crystallization and polymorphic transformation of fats and fatty acids. In: Garti N, Sato K, editors. Crystallization and polymorphism of fats and fatty acids. New York: Marcel Dekker; 1988. p. 267–304.
Yung C, Hung C. Entrapment and release of saquinavir using novel cationic solid lipid nanoparticles. Int J Pharm. 2009;365(1–2):206–13.
Alex M, Chacko A, Jose A, Souto E. Lopinavir loaded solid lipid nanoparticles for intestinal lymphatic targeting. Eur J Pharm Sci. 2011;42(1–2):11–8.
Uner M. Preparation, characterization and physico-chemical properties of solid lipid nanoparticles and nanostructured lipid carriers: their benefits as colloidal drug carrier systems. Pharmazie. 2006;61:375–86.
Kerstin T, Carsten K, Sameti M, Carsten O, Muller. Transfection with different colloidal systems: comparison of solid lipid nanoparticles and liposomes. J Control Rel. 2004;97(2):321–32.
Balaji S, Balaji P. Nanotechnology and cancer—an overview. Int J Pharm Biopharm. 2010;1(4):186–201.
Jiesheng Y, Wang Q, Xuefeng Z, Zhang N. Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis. Int J Pharm. 2008;352(1–2):273–9.
Muller R, Runge S. Solid lipid nanoparticles for controlled drug delivery. In: Benita S, editor. Submicron emulsions in drug targeting and delivery. Amsterdam: Harwood Academic; 1998. p. 219–34.
Couvreur P, Kante B, Grislain L. Toxicity of poly alkyl cyano acrylate nanoparticles II: doxorubicin-loaded nanoparticles. J Pharm Sci. 1982;71:790–2.
Kreuter J. Nanopaticles based drug delivery systems. J Control Rel. 1991;16:169–76.
Roberta C, Rosa G, Patrizia C, Burgalassi S, Fabrizio M. Solid lipid nanoparticles as ocular delivery system for tobramycin. Int J Pharm. 2002;238(1–2):241–5.
Alvarez R, Naik A, Kalia Y, Guy R, Fessi H. Skin penetration and distribution of polymeric nanoparticles. J Control Rel. 2004;99(1):53–62.
Magenheim B, Levy M, Benita S. A new in vitro technique for evaluation of drug release profile from colloidal carriers—ultrafiltration technique at low pressure. Int J Pharm. 1993;94:115–23.
Benita S, Friedmann D, Weinstock M. Physiostigmine emulsions: a new injectable controlled release delivery system. Int J Pharm. 1986;30:47–55.
Benita S, Friedmann D, Weinstock M. Pharmacological evaluation of an injectable prolonged release emulsion of physiostigmine in rabbits. J Pharm Pharmacol. 1986;38:653–8.
Eldem T, Speiser P, Hincal A. Optimization of spray-dried and congealed lipid microparticles and characterization of their surface morphology by scanning electron microscopy. Pharm Res. 1991;8:47–54.
Souto E, Muller R. The use of SLN and NLC as topical particulate carriers for imidazole antifungal agents. Pharmazie. 2006;61:431–7.
Lippacher A, Muller R, Mader K. Liquid and semisolid SLN™ dispersions for topical application: rheological characterization. Eur J Pharm Biopharm. 2004;58(3):561–7.
Lippacher A, Muller R, Mader K. Preparation of semisolid drug carriers for topical application based on solid lipid nanoparticles. Int J Pharm. 2001;214(1–2):9–12.
Jahnke S. The theory of high pressure homogenization. In: Muller RH, Benita S, Bohm B, editors. Emulsions and nanosuspensions for the formulation of poorly soluble drugs. Stuttgart: Medpharm; 1998. p. 177–200.
Gasco M. Method for producing solid lipid microspheres having a narrow size distribution. US: United States patent; 1993. 188837.
Serpe L, Canaparo R, Daperno M, Sostegni R, Gasco M, Zara G. Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model. Eur J Pharm Sci. 2010;39(5):428–36.
Rodriguez A, Solinis M, Gascon A, Pedraz J. Short- and long-term stability study of lyophilized solid lipid nanoparticles for gene therapy. Eur J Pharm Biopharm. 2009;71(2):181–9.
Kirsten W, Siekmann B. Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles. Int J Pharm. 1997;151(1):35–45.
Wook K, Chun M, Subedi R, Sang A, Yoon J, Choi H. Doxorubicin-loaded solid lipid nanoparticles to overcome multidrug resistance in cancer therapy. Nanomedicine Nanotechnol Biol M. 2010;6(2):210–3.
Chattopadhyay P, Shekunov BY, Yim D, et al. Production of solid lipid nanoparticles suspensions using supercritical fluid extraction of emulsions (SFEE) for pulmonary delivery using the AERx system. Adv Drug Deliv Rev. 2007;6:444–53.
Sellers S, Clark G, Sievers R, Carpenter J. Dry powders of stable protein formulations from aqueous solutions prepared using supercritical CO2-assisted erosolization. J Pharm Sci. 2001;90:785–97.
Jovanovic N, Bouchard A, Hofland G, Witkamp G, et al. Stabilization of proteins in dry powder formulations using supercritical fluid technology. Pharm Res. 2004;21:1955–69.
Rodrigues M, Peiriço N, Matos M, Lobato, et al. Microcomposites theophylline/hydrogenated palm oil from a PGSS process for controlled drug delivery systems. J Supercrit Fluids. 2004;29:175–84.
Jung J, Perrut M. Particle design using supercritical fluids: literature and patent survey. J Supercrit Fluids. 2001;20:179–219.
Salmaso S, Elvassore N, Bertucco A, et al. Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process. J Pharm Sci. 2009;98:640–9.
Sebti T, Amighi K. Preparation and in vitro evaluation of lipidic carriers and fillers for inhalation. Eur J Pharm Biopharm. 2006;63:51–8.
Seetapan N, Bejrapha P, Srinuanchai W. Rheological and morphological characterizations on physical stability of gamma-oryzanol-loaded solid lipid nanoparticles. Micron. 2010;41(1):51–8.
Borgstrom B. Importance of phospholipids, pancreatic phospholipase A2, and fatty acid for the digestion of dietary fat: in vitro experiments with the porcine enzymes. Gastroenterol. 1980;78:954–62.
Libo W, Zhang J, Watanabe W. Physical and chemical stability of drug nanoparticles. Adv Drug Del Rev. 2011;63(6):456–69.
Muller R, Runge S, Ravelli V, Thunemann A, Mehnert W, Souto E. Cyclosporine-loaded solid lipid nanoparticles (SLN®): drug–lipid physicochemical interactions and characterization of drug incorporation. Eur J Pharm Biopharm. 2008;68(3):535–44.
Muhlen A, Muhlen E, Niehus H, Mehnert W. Characterisation of solid lipid nanoparticles by atomic force microscopy. Eur J Pharm Sci. 1994;2(1–2):178.
Muller R, Freitas C, Muhlen A, Mehnert W. Solid lipid nanoparticles for controlled drug delivery. Eur J Pharm Sci. 1996;4(1):S75.
Scheffel U, Rhodes B, Natajaran T, Wagner H. Albumin microspheres for study of the reticuloendothelial system. J Nucl Med. 1970;13:498–503.
Indu PK, Rohit B, Swati B, Vandita K. Potential of solid lipid nanoparticles in brain targeting. J Control Rel. 2008;127:97–109.
Volkhard J, Mader K, Gohla S. Solid lipid nanoparticles (SLN™) based on binary mixtures of liquid and solid lipid: a 1H-NMR study. Int J Pharm. 2000;205(1–2):15–21.
Acosta E. Bioavailability of nanoparticles in nutrient and nutraceutical delivery. Current Opin Colloid Interface Sci. 2009;14(1):3–15.
Ahlin P, Kristl J, Kobar S. Optimization of procedure parameters and physical stability of solid lipid nanoparticles in dispersion. Acta Pharm. 1998;48:257–67.
Ahmadian S, Fakhree A. Lipid based nanoparticles containing saturated solution of NaCl, may be used to targeted eradication of cancerous cells. Biosci Hypotheses. 2009;2(3):172–3.
Qingzhi L, Aihua Y, Yanwei X, Houli L, Zhimei S, Fengliang C, Guangxi Z. Development and evaluation of penciclovir-loaded solid lipid nanoparticles for topical delivery. Int J Pharm. 2009;372(1–2):191–8.
Radomska A. Stability of lipid excipients in solid lipid nanoparticles. Adv Drug Del Rev. 2007;59(6):411–8.
Scholer N, Hahn H, Muller R, Liesenfeld O. Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages. Int J Pharm. 2002;231(2):167–76.
Xiong S, Yang H, Yin X, Zhao R. Mitoxantrone-loaded BSA nanospheres and chitosan nanospheres for local injection against breast cancer and its lymph node metastases. II: Tissue distribution and pharmacodynamics. Int J Pharm. 2006;307(2):175–81.
Low S, Henne A, Doorneweerd D. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2008;41:120–9.
Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen Y, Dai J. Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer Res. 2008;68:6652–60.
Chien J, Illi A, Ko H, Korn M, Fong L, Chen M. A Phase I study of a 2-day lapatinib hemosensitization pulse preceding nanoparticles albumin-bound paclitaxel for advanced solid malignancies. Clin Cancer Res. 2009;15:5569–75.
Zhu L, Huo L, Wang L, Tong X, Xiao Y. Targeted delivery of methotrexate to skeletal muscular tissue by thermosensitive magnetoliposomes. Int J Pharmacol. 2009;370:136–43.
Conlin K, Seidman D, Bach A. Phase II trial of weekly nanoparticles albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. Clin Breast Cancer. 2010;10:281–7.
Keon K, Myung C, Subedi R, Sang A, Jung Y, Hoo C. Doxorubicin-loaded solid lipid nanoparticles to overcome multidrug resistance in cancer therapy. Nanomedicine: Nanotechnol Biol Med. 2010;6(2):210–3.
Eyles J, Carpenter Z, Alpar H, Williamson E. Immunological aspects of polymer microsphere vaccine delivery systems. J Drug Target. 2003;11:509–14.
Tamber H, Johansen P, Merkle H, Gander B. Formulation aspects of biodegradable polymeric microspheres for antigen delivery. Adv Drug Deliv Rev. 2005;57:357–76.
Storni T, Kündig T, Senti G, Johansen P. Immunity in response to particulate antigen-delivery systems. Adv Drug Deliv Rev. 2005;57:333–55.
Weiss J, Decker E, McClements D, et al. Solid lipid nanoparticles as delivery systems for bioactive food components. Food Biophys. 2008;3:146–54.
Mei Z, Li X, Wu Q, et al. The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle. Pharm Res. 2005;51:345–51.
Rodriguez A, Delgado D, Solinis M, et al. Lipid nanoparticles as vehicles for macromolecules: nucleic acids and peptides. Recent Pat Drug Deliv Formul. 2011;5:214–26.
Elsabahy M, Nazarali A, Foldvari M. Non-viral nucleic acid delivery: key challenges and future directions. Curr Drug Deliv. 2011;8:235–44.
Wagner V, Dullaart A, Bock A, Zweck A. The emerging nanomedicine landscape. Nature Biotech. 2006;24(10):1211–7.
Silva A, Gonzalez E, Garcia M, Egea M, Fonseca J, Silva R. Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound. Colloids Surfaces B: Biointerfaces. 2011;86(1):158–65.
Silva A, Santos D, Ferreira D, Souto E. Characterization of ibuprofen loaded solid lipid nanoparticles dispersed in semi-solid Carbopol gels. J Biotech. 2007;131(2):S67–8.
Subedi R, Kang K, Choi H. Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin. Eur J Pharm Sci. 2009;37(3–4):508–13.
Liu F, Park Y, Zhang Y, Conwell C, Liu Y, Bathula R, Huang L. Targeted cancer therapy with novel high drug-loading nanocrystals. J Pharm Sci. 2010;99:3542–51.
Khdair A, Chen D, Patil Y, Dou P, Shekhar P, Panyam J. Nano particle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance. J Control Rel. 2010;141:137–44.
Yu Y, Kim E, Park D, Shim G, Lee S, Kim Y, Kim C, Oh Y. Cationic solid lipid nanoparticles for co-delivery of paclitaxel and siRNA. Eur J Pharm Biopharm. 2012;80(2):268–73.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mishra, D.K., Dhote, V., Bhatnagar, P. et al. Engineering solid lipid nanoparticles for improved drug delivery: promises and challenges of translational research. Drug Deliv. and Transl. Res. 2, 238–253 (2012). https://doi.org/10.1007/s13346-012-0088-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13346-012-0088-9