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AAPS PharmSciTech

, Volume 6, Issue 2, pp E158–E166 | Cite as

Etoposide-loaded nanoparticles made from glyceride lipids: Formulation, characterization, in vitro drug release, and stability evaluation

Article

Abstract

The aim of the study was to prepare etoposide-loaded nanoparticles with glyceride lipids and then characterize and evaluate the in vitro steric stability and drug release characteristics and stability. The nanoparticles were prepared by melt emulsification and homogenization followed by spray drying of nanodispersion. Spray drying created powder nanoparticles with excellent redispersibility and a minimal increase in particle size (20–40 nm). Experimental variables, such as homogenization pressure, number of homogenization cycles, and surfactant concentration, showed a profound influence on the particle size and distribution. Spray drying of Poloxamer 407-stabilized nanodispersion lead to the formation of matrix-like structures surrounding the nanoparticles, resulting in particle growth. The in vitro steric stability test revealed that the lipid nanoparticles stabilized by sodium tauroglycocholate exhibit excellent steric stability compared with Poloxamer 407. All 3 glyceride nanoparticle formulations exhibited sustained release characteristics, and the release pattern followed the Higuchi equation. The spray-dried lipid nanoparticles stored in black polypropylene containers exhibited excellent long-term stability at 25°C and room light conditions. Such stable lipid nanoparticles with in vitro steric stability can be a beneficial delivery system for intravenous administration as long circulating carriers for controlled and targeted drug delivery.

Keywords

lipid nanoparticles high-pressure homogenization spray drying Poloxamer 407 steric stability 

References

  1. 1.
    Muller RH, Olbrich C. Solid lipid nanoparticles: phagocytic uptake, in vitro cytoxicity and in vitro biodegradation.Drugs Made in Germany. 1999;42:49–53.Google Scholar
  2. 2.
    Lim SJ, Kim CK. Formulation parameters determining the physicochemical characteristics of solid lipid nanoparticles loaded with all-trans retinoic acid.Int J Pharm. 2002;243:135–146.CrossRefGoogle Scholar
  3. 3.
    Freitas C, Muller RH. Spray drying of solid lipid nanoparticles (SLN TM).Eur J Pharm Biopharm. 1998;46:145–151.CrossRefGoogle Scholar
  4. 4.
    Magenheim B, Levy MY, 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;94:115–123.CrossRefGoogle Scholar
  5. 5.
    Muller RH, Ruhl D, Runge S, Schulze-Foster K, Mehnert W. Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant.Pharm Res. 1997;14:458–462.CrossRefGoogle Scholar
  6. 6.
    zur Muhlen 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.CrossRefGoogle Scholar
  7. 7.
    Muller RH, Maassen S, Weyhers H, Mehnert W. Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407.J Drug Target. 1996;4:161–170.CrossRefGoogle Scholar
  8. 8.
    Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery II. Drug incorporation and physicochemical characterization.J Microencapsul. 1999;16:205–213.CrossRefGoogle Scholar
  9. 9.
    Schwarz C, Mehnert W, Lucks JS, Muller RH. Solid lipid nanoparticles (SLN) for controlled drug delivery I: production, characterization and sterilization.J Control Release. 1994;30:83–96.CrossRefGoogle Scholar
  10. 10.
    Siekmann B, Westesen K. Thermoanalysis of the recrystallization process of melt-homogenized glyceride nanoparticles.Colloid Surf B: Biointerfac. 1994;3:159–175.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    Bunjes H, Drechsler M, Koch MHJ, Westesen K. Incorporation of the model drug ubidecarenone into solid lipid nanoparticles.Pharm Res. 2001;18:287–293.CrossRefGoogle Scholar
  13. 13.
    Bunjes H, Koch MHJ, Westesen K. Effect of surfactants on the crystallization and polymorphism of lipid nanoparticles.Progr Colloid Polym Sci. 2002;121:7–10.CrossRefGoogle Scholar
  14. 14.
    Bunjes H, Koch MHJ, Westesen K. Influence of emulsifiers on the crystallization of solid lipid nanoparticles.J Pharm Sci. 2003;92:1509–1520.CrossRefGoogle Scholar
  15. 15.
    Bunjes H, Koch MHJ, Westesen K. Effect of particle size on colloidal solid triglycerides.Langmuir. 2000;16:5234–5241.CrossRefGoogle Scholar
  16. 16.
    Freitas C, Muller RH. Correlation between long-term stability of nanoparticles (SLN) and crystallinity of the lipid phase.Eur J Pharm Biopharm. 1999;47:125–132.CrossRefGoogle Scholar
  17. 17.
    Zimmerman E, Muller RH, Mader K. Influence of different parameters on reconstitution of lyophilized SLN.Int J Pharm. 2000;196:211–213.CrossRefGoogle Scholar
  18. 18.
    Bodmeier R, Chen H. Preparation of biodegradable poly(+/−) lactide microparticles using a spray drying technique.J Pharm Pharmacol. 1988;40:754–757.Google Scholar
  19. 19.
    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.CrossRefGoogle Scholar
  20. 20.
    Forni F, Coppi G, Vandelli MA, Cameroni R. Drug release from spray-dried and spray-embedded microparticles of diltiazem hydrochloride.Chem Pharm Bull. 1991;39:2091–2095.Google Scholar
  21. 21.
    Moghimi SM, Porter CJH, Muir IS, Illum L, Davis SS, Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating.Biochem Biophys Res Commun. 1991;127:861–866.CrossRefGoogle Scholar
  22. 22.
    Porter CJH, Moghimi SM, Illum L, Davis SS. The polyoxyethylene/polyoxypropylene block co-polymer poloxamer 407 selectively redirects intravenously injected microspheres to sinusoidal endothelial cells of rabbit bone marrow.FEBS Lett. 1992;305:62–66.CrossRefGoogle Scholar
  23. 23.
    Artursson P, Illum L, Davis SS. The fate of microparticulate drug carriers after intravenous administration. In:Polymers in controlled drug delivery. Bristol, London: Butterworth-Heinemann. 1987;15–24.Google Scholar
  24. 24.
    Lin W, Coombes AGA, Garnett MC, et al. Preparation of sterically stabilized human serum albumin nanospheres using a novel Dextranox-MPEG crosslinking agent.Pharm Res. 1994;11:1589–1592.Google Scholar
  25. 25.
    Olbrich C, Kayser O, Muller RH. Lipase degradation of Dynasan 114 and 116 solid lipid nanoparticles (SLN)—effect of surfactants, storage time and crystallinity.Int J Pharm. 2002;237:119–128.CrossRefGoogle Scholar
  26. 26.
    Jenning V, Lippacher A, Gohla SH. Medium scale production of solid lipid nanoparticles (SLN) by high pressure homogenization.J Microencapsul. 2002;19:1–10.CrossRefGoogle Scholar
  27. 27.
    Yang SC, Lu LF, Cai Y, Zhu JB, Liang BW, Yang CZ. Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.J Control Release. 1999;59:299–307.CrossRefGoogle Scholar
  28. 28.
    Muller RH, Ruhl D, Runge SA. Biodegradation of solid lipid nanoparticles as a function of lipase incubation time.Int J Pharm. 1996;144:115–121.CrossRefGoogle Scholar
  29. 29.
    Siekmann B, Westesen K. Submicron-sized parenteral carrier systems based on solid lipids.Pharm Pharmacol Lett. 1992;1:123–126.Google Scholar
  30. 30.
    Young TJ, Johnston KP, Pace GW, Mishra AK. Phospholipi-stabilized nanoparticles of cyclosporine A by rapid expansion from supercritical to aqueous solution.AAPS Pharm Sci Tech. 2004;5(1):Article 11. Available at: <http://www.aapspharmscitech.org.>Google Scholar
  31. 31.
    Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery.J Control Release. 2002;82:189–212.CrossRefGoogle Scholar
  32. 32.
    Reddy LH, Murthy RSR. Polymerization of n-butyl cyanoacrylate in presence of surfactant: study of influence of polymerization factors on particle properties, drug loading and evaluation of its drug release kinetics.ARS Pharmaceutica. 2003;44:351–369.Google Scholar
  33. 33.
    Schwarz C, Freitas C, Mehnert W, Muller RH. Sterilization and physical stability of drug-free and etomidate-loaded solid lipid nanoparticles.Proc Int Symp Cont Rel Bioact Mater. 1995;22:766–767.Google Scholar
  34. 34.
    Bunjes H, Westesen K, Koch MHJ. Crystallization tendency and polymorphic transitions in triglyceride nanoparticles.Int J Pharm. 1996;129:159–173.CrossRefGoogle Scholar
  35. 35.
    Westesen K, Bunjes H. Do nanoparticles prepared from lipids solid at room temperature always possess a solid lipid matrix?Int J Pharm. 1995;115:129–131.CrossRefGoogle Scholar
  36. 36.
    Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice.Pharmacol Rev. 2001;53:283–318.Google Scholar
  37. 37.
    Hamdani J, Moes AJ, Amighi K. Physical and thermal characterisation of Precirol and Compritol as lipophilic glycerides used for the preparation of controlled-release matrix pellets.Int J Pharm. 2003;260:47–57.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2005

Authors and Affiliations

  1. 1.Drug Delivery Research Laboratory, Center of Relevance and Excellence in New Drug Delivery Systems (NDDS), Pharmacy Department, G H Patel Building, Donor’s PlazaMS UniversityBarodaIndia

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