A review on Solid Lipid Nanoparticles (SLN) for controlled and targeted delivery of medicinal agents
Abstract
Solid lipid nanoparticles (SLN) were introduced as alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro- and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. Nanoparticles are sub-nanosized colloidal structures composed of synthetic or semi synthetic polymer. The colloidal carriers based on biodegradable and biocompatible polymeric system have largely influenced the controlled and targeted drug delivery concept. Nanoparticle loaded bioactive could not only deliver drug to specific organ within the body but delivery rate in addition could be controlled as being bystanders, burst, controlled pulsatile or modulated. This paper reviews the present methods and techniques regarding production of SLN, drug incorporation, loading capacity and drug release, especially focusing on drug release mechanisms. Relevant issues for the introduction of SLN to the pharmaceutical market, such as status of excipient, toxicity/tolerability aspects and sterilization and long-term stability including industrial large scale production are also discussed. The potential of SLN to be exploited for the different administration routes is highlighted.
Keywords:
Colloidal drug carrier, Nanotechnology, Solid lipid nanoparticles, Targeted drug delivery.
References
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34. Chen F, Zhang ZR, Huang Y. Evaluation and modification of Ntrimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm. 2007; 336: 166–173.
35. Sarmento B, Ferreira D, Veiga F, Ribeiro A. Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pregelation through DSC and FTIR studies. Carbo Poly. 2006; 66: 1–7.
36. Maaûen S, Schwarz C, Mehnert W, Lucks JS, Specht FY, MuÈller BW, MuÈller RH. Comparison of cytotoxicity between polyester nanoparticles and solid lipid nanoparticles (SLN). Proc Int Symp Control Release Bioact Mater. 1993; 20: 490-491.
37. Weyhers H, Ehlers S, Mehnert W, Hahn H, MuÈller RH. Solid lipid nanoparticles: determination of in vivo toxicity. Proc 1st World Meeting APGI/APV. 1995; 489-490.
38. FundaroÁ A, Cavalli R, Bargoni A, Vighetto D, Zara GP, Gasco MR. Non-stealth and stealth solid lipid nanospheres carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats. Pharm Res. 2000; 42(4): 337-343.
39. MuÈller RH, Dingler A. The next generation after the liposomes: solid lipid nanoparticles (SLNe, Lipopearlse) as dermal carrier in cosmetics. Eurocosmetics. 1998; 7/8: 19-26.
40. Wissing S, MaÈder K, Rogaschewski S, MuÈller RH. Solid lipid nanoparticles (SLN): a novel carrier for UV-blockers. Int J Pharm. 2001; 56: 783-786.
41. Florence AT. Nanoparticle uptake by the oral route: fulfilling its potential. Drug Discov Today Technol. 2005; 2: 75–81.
42. Pinto JF, MuÈller RH. Pellets as carriers of solid lipid nanoparticles (SLN) for oral administration of drugs. Die Pharmazie. 1999; 506- 509.
43. Galindo-Rodriguez SA, Allemann E, Fessi H, Doelker E. Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Crit Rev Ther Drug Carr Syst. 2005; 22: 419–464.
44. Cavalli R, Bocca C, Miglietta A, Caputo O, Gasco MR. Albumin adsorption on stealth and non-stealth solid lipid nanoparticles. STP Pharma Sci. 1999; 9: 183-189.
45. Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharke-vich DA, Kreuter J. Delivery of loperamide across the blood-brain barrier with Polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res. 1997; 14: 325-328.
46. Borges O, Borchard G, Verhoef JC, Sousa AD, Junginger HE. Preparation of coated nanoparticles for a new mucosal vaccine delivery system. Int J Pharm. 2005; 299: 155–166.
47. Borgesa O, Tavaresb J, Sousaa AD, Borchardc G, Hans E, Jungingerd HE. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate coated chitosan nanoparticles. Eur J Pharm Sci. 2007; 32: 278–290.
2. MuÈller RH, Maauen S, Weyhers H, Specht F, Lucks JS. Cytotoxicity of magnetite loaded polylactide, polylactidecoglycolide particles and solid lipid nanoparticles (SLN). Int J Pharm. 1996; 138: 85-94.
3. Gasco MR. Method for producing solid lipid microspheres having a narrow size distribution. US Patent 5. 1993; 250: 236.
4. Eldem T, Speiser P, Hincal A. Optimization of spray-dried and congealed lipid micropellets and characterization of their surface morphology by scanning electron microscopy. Pharm Res. 1991; 8: 47-54.
5. MuÈller RH, Schwarz C, Mehnert W, Lucks JS. Production of solid lipid nanoparticles (SLN) for controlled drug delivery. Proc Int Symp Control Release Bioact Mater. 1993; 20: 480-481.
6. Gasco MR. Solid lipid nanospheres from warm microemulsions. Pharm Technol Eur. 1997; 9: 52-58.
7. Boltri L, Canal T, Esposito PA, Carli F. Lipid nanoparticles: evaluation of some critical formulation parameters. Proc Int Symp Control Release Bioact Mater. 1993; 20: 346-347.
8. Morel S, Terreno E, Ugazio E, Aime S, Gasco MR. NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium (III) complexes. Eur J Pharm Biopharm. 1998; 45: 157-163.
9. Carli F. Physical Chemistry and Oral Absorption of the Nanoparticulate Systems. Rencentre Pharmapeptides. 1999.
10. Schwarz C, Mehnert W, Lucks JS, MuÈller RH. Solid lipid nanoparticles (SLN) for controlled drug delivery: production, characterization and sterilization. J Control Release. 1994; 30: 83-
96. 11. Domb AJ. Lipospheres for controlled delivery of substances. US Patent 5. 1993; 188: 837.
12. Domb AJ, Marlinsky A, Maniar M, Teomim L. Insect repellent formulations of N,N-diethyl-m-toluamide (deet) in a liposphere system: efficacy and skin uptake. J Am Mosquito Control Assoc. 1995; 11: 29-34.
13. Domb AJ. Long acting injectable oxytetracycline-liposphere formulations. Int J Pharm. 1995; 124: 271-278.
14. Westesen K, Siekmann B. Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles. Int J Pharm. 1997; 151: 35-45.
15. Siekmann B, Westesen K. Investigations on solid lipid nanoparticles prepared by precipitation in o/w emulsions. Eur J Pharm Biopharm. 1996; 43: 104-109.
16. Westesen K, Bunjes H, Koch MHJ. Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. J Control Release. 1997; 48: 223-236.
17. Schwarz C, Freitas C, Mehnert W, MuÈller RH. Sterilisation and physical stability of drug free and etomidate loaded solid lipid nanoparticles. Proc Int Symp Control Release Bioact Mater. 1995; 22: 766-767.
18. Jenning V, Gysler A, SchaÈfer-Korting M, Gohla S. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug penetration into porcine skin. Eur J Pharm Biopharm. 2000; 49(3): 211-218.
19. Jenning V, SchaÈfer-Korting M, Gohla S. Vitamin A loaded solid lipid nanoparticles for topical application: drug release properties. J Control Release. 2000; 66: 115-126.
20. Penkler L, MuÈller RH, Runge SA, Ravelli V. Pharmaceutical cyclosporin formulation with improved biopharmaceutical properties: improved physical quality and greater stability and method for producing said formulation. WO 99/56733. 1999.
21. Westesen K, Siekmann B, Koch MHJ. Investigations on the physical state of lipid nanoparticles by synchrotron radiation X-ray diffraction. Int J Pharm. 1993; 93: 189-199.
22. Bunjes H, Westesen K, Koch MHJ. Crystallization tendency and polymorphic transitions in triglyceride nanoparticles. Int J Pharm. 1996; 129: 159-173.
23. Jenning V, Gohla S. Solid lipid nanoparticles (SLN) based on binary mixtures of liquid and solid lipids: a 1H-NMR study. Int J Pharm. 2000; 205: 15-21.
24. Jenning V, Gohla S. Characterisation of solid lipid nanoparticles (SLN) based on binary mixtures of liquid and solid lipids. Int J Pharm. 2000; 199: 167-177.
25. Cavalli R, Peira E, Caputo O, Gasco MR. Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with bcyclodextrins. Int J Pharm. 1999; 182: 59-69.
26. MuÈhlen A, Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery- drug release and release mechanism. Eur J Pharm Biopharm. 1998; 45: 149-155.
27. Garti N, Sato K. Crystallization and Polymorphism of Fats and Fatty Acids. Marcel Dekker. New York and Basel (1998) 125-129.
28. Anger S, Caldwell K, Niehus H, MuÈller RH. High resolution size determination of 20 nm colloidal gold particles by sedimentation field flow fractionation. Pharm Res. 1999; 16: 1743-1747.
29. Anger S, Caldwell KD, MuÈller RH. Characterization of molecular, colloids and Particles with field-flow fractionation. Pharm Ind. 2000; 62: 150-156.
30. Anger S, Mehnert W, Caldwell K, MuÈller RH. High resolution determination of adsorption layer mass on particles by sedimentation field-flow fractionation. Proc. 2nd World Meeting APGI/ APV.1998; 643-644.
31. Anger S, Caldwell K, Mehnert W, MuÈller RH. Coating of nanoparticles: analysis of adsorption using sedimentation field-flow fractionation (SdFFF). Proc Int Symp Control Release Bioact Mater. 1999;
26. 32. León TL, Carvalho ELS, Seijo B, Vinuesa JLO, González DB. Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behavior. J Colloid Interface Sci. 2005; 283: 344–351.
33. Banerjee T, Mitra S, Singh AK, Sharma RK, Maitra A. Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int J Pharm. 2002; 243: 93–105.
34. Chen F, Zhang ZR, Huang Y. Evaluation and modification of Ntrimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm. 2007; 336: 166–173.
35. Sarmento B, Ferreira D, Veiga F, Ribeiro A. Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pregelation through DSC and FTIR studies. Carbo Poly. 2006; 66: 1–7.
36. Maaûen S, Schwarz C, Mehnert W, Lucks JS, Specht FY, MuÈller BW, MuÈller RH. Comparison of cytotoxicity between polyester nanoparticles and solid lipid nanoparticles (SLN). Proc Int Symp Control Release Bioact Mater. 1993; 20: 490-491.
37. Weyhers H, Ehlers S, Mehnert W, Hahn H, MuÈller RH. Solid lipid nanoparticles: determination of in vivo toxicity. Proc 1st World Meeting APGI/APV. 1995; 489-490.
38. FundaroÁ A, Cavalli R, Bargoni A, Vighetto D, Zara GP, Gasco MR. Non-stealth and stealth solid lipid nanospheres carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats. Pharm Res. 2000; 42(4): 337-343.
39. MuÈller RH, Dingler A. The next generation after the liposomes: solid lipid nanoparticles (SLNe, Lipopearlse) as dermal carrier in cosmetics. Eurocosmetics. 1998; 7/8: 19-26.
40. Wissing S, MaÈder K, Rogaschewski S, MuÈller RH. Solid lipid nanoparticles (SLN): a novel carrier for UV-blockers. Int J Pharm. 2001; 56: 783-786.
41. Florence AT. Nanoparticle uptake by the oral route: fulfilling its potential. Drug Discov Today Technol. 2005; 2: 75–81.
42. Pinto JF, MuÈller RH. Pellets as carriers of solid lipid nanoparticles (SLN) for oral administration of drugs. Die Pharmazie. 1999; 506- 509.
43. Galindo-Rodriguez SA, Allemann E, Fessi H, Doelker E. Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Crit Rev Ther Drug Carr Syst. 2005; 22: 419–464.
44. Cavalli R, Bocca C, Miglietta A, Caputo O, Gasco MR. Albumin adsorption on stealth and non-stealth solid lipid nanoparticles. STP Pharma Sci. 1999; 9: 183-189.
45. Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharke-vich DA, Kreuter J. Delivery of loperamide across the blood-brain barrier with Polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res. 1997; 14: 325-328.
46. Borges O, Borchard G, Verhoef JC, Sousa AD, Junginger HE. Preparation of coated nanoparticles for a new mucosal vaccine delivery system. Int J Pharm. 2005; 299: 155–166.
47. Borgesa O, Tavaresb J, Sousaa AD, Borchardc G, Hans E, Jungingerd HE. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate coated chitosan nanoparticles. Eur J Pharm Sci. 2007; 32: 278–290.
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Parashar, A. K., D. Kakde, V. Chadhar, R. Devaliya, V. Shrivastav, and U. K. Jain. “A Review on Solid Lipid Nanoparticles (SLN) for Controlled and Targeted Delivery of Medicinal Agents”. Current Research in Pharmaceutical Sciences, Vol. 1, no. 2, Dec. 2011, pp. 37-47, https://crpsonline.com/index.php/crps/article/view/34.
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