Skip to main content
NCBI home page
AAPS PharmSciTech logoLink to AAPS PharmSciTech
. 2007 Mar 23;8(1):E162–E170. doi: 10.1208/pt0801024

Preparation, characterization, and in vitro and in vivo evaluation of lovastatin solid lipid nanoparticles

Gande Suresh 1,✉, Kopparam Manjunath 1, Vobalaboina Venkateswarlu 1,✉, Vemula Satyanarayana 2
PMCID: PMC2750435  PMID: 17408223

Abstract

The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin solid lipid nanoparticles (SLN) duodenally to rats. Lovastatin SLN were developed using triglycerides by hot homogenization followed by ultrasonication. Particle size and zeta potential were measured by photon correlation spectroscopy. The solid state of the drug in the SLN and lipid modification were characterized. Bioavailability studies were conducted in male Wistar rats after intraduodenal administration of lovastatin suspension and SLN. Stable lovastatin SLN having a mean size range of 60 to 119 nm and a zeta potential range of −16 to −21 mV were developed. More than 99% of the lovastatin was entrapped in the SLN. Lovastatin was dispersed in an amorphous state, and triglycerides were in {ieE162-1} form in the SLN. In vitro stability studies showed the slow release and stability of lovastatin SLN. The relative bioavailabilities of lovastatin and lovastatin hydroxy acid of SLN were increased by ∼173% and 324%, respectively, compared with the reference lovastatin suspension.

Keywords: Solid lipid nanoparticles, lovastatin, differential scanning calorimetry, powder x-ray

Full Text

The Full Text of this article is available as a PDF (426.4 KB).

References

  • 1.Yang S, Zhu J, Lu Y, Liang B, Yang C. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm Res. 1999;16:751–757. doi: 10.1023/A:1018888927852. [DOI] [PubMed] [Google Scholar]
  • 2.Lennernas H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet. 1997;32:403–425. doi: 10.2165/00003088-199732050-00005. [DOI] [PubMed] [Google Scholar]
  • 3.Khoo SM, Humberstone AJ, Porter CJH, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm. 1998;167:155–164. doi: 10.1016/S0378-5173(98)00054-4. [DOI] [Google Scholar]
  • 4.Hauss DJ, Fogal SE, Ficorilli JV, et al. Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water soluble LTB4 inhibitor. J Pharm Sci. 1998;87:164–169. doi: 10.1021/js970300n. [DOI] [PubMed] [Google Scholar]
  • 5.Delie F. Evaluation of nano-and microparticle uptake by the gastrointestinal tract. Adv Drug Deliv Rev. 1998;34:221–233. doi: 10.1016/S0169-409X(98)00041-6. [DOI] [PubMed] [Google Scholar]
  • 6.Bargoni A, Cavalli R, Caputo O, Fundaro A, Gasco MR, Zara GP. Solid lipid nanoparticles in lymph and plasma after duodenal administration to rats. Pharm Res. 1998;15:745–750. doi: 10.1023/A:1011975120776. [DOI] [PubMed] [Google Scholar]
  • 7.Eldridge JH, Hammond CJ, Meulbrock JA, Staas JK, Gilley RM, Tice TR. Controlled vaccine release in the gut-associated lymphoid tissue, I: orally administered biodegradable microspheres target the Peyer's patches. J Control Release. 1990;11:205–214. doi: 10.1016/0168-3659(90)90133-E. [DOI] [Google Scholar]
  • 8.Pappo J, Ermak TM, Steger HJ. Monoclonal antibody directed targeting of fluorescent polystyrene microspheres to Peyer's patch M cells. Immunology. 1991;73:277–280. [PMC free article] [PubMed] [Google Scholar]
  • 9.Jepson MA, Simmons NL, O'Hagan DT, Hirst BH. Comparison of poly(DL-lactide-co-glycolide) and polystyrene microsphere targeting to intestinal M cells. J Drug Target. 1993;1:245–249. doi: 10.3109/10611869308996082. [DOI] [PubMed] [Google Scholar]
  • 10.Nishioka Y, Yoshino H. Lymphatic targeting with nanoparticulate system. Adv Drug Deliv Rev. 2001;47:55–64. doi: 10.1016/S0169-409X(00)00121-6. [DOI] [PubMed] [Google Scholar]
  • 11.Cavalli R, Bargoni A, Podio V, Muntoni E, Zara GP, Gasco MR. Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin. J Pharm Sci. 2003;92:1085–1094. doi: 10.1002/jps.10368. [DOI] [PubMed] [Google Scholar]
  • 12.Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Control Release. 2004;95:627–638. doi: 10.1016/j.jconrel.2004.01.005. [DOI] [PubMed] [Google Scholar]
  • 13.Wu Y, Zhao J, Henion J, Korfmacher WA, Lapiguera AP, Lin CC. Microsample determination of lovastatin and its hydroxy acid metabolite in mouse and rat plasma by liquid chromatography/ionspray tandem mass spectrometry. J Mass Spectrom. 1997;32:379–387. doi: 10.1002/(SICI)1096-9888(199704)32:4<379::AID-JMS461>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  • 14.Rajh SJ, Kreft S, Strukelj B, Vrecer F. Comparison of CE and HPLC methods for determining lovastatin and its oxidation products after exposure to an oxidative atmosphere. Croat Chem Acta. 2003;76:263–268. [Google Scholar]
  • 15.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. doi: 10.1016/0378-5173(93)90177-H. [DOI] [Google Scholar]
  • 16.Staggers JE, Hernell O, Stafford RJ, Carey MC. Physical-chemical behaviour of dietary and biliary lipids during intestinal digestion and absorption, I: phase behavior and aggregation states of model lipid systems patterned after aqueous duodenal contents of healthy adult human beings. Biochemistry. 1990;29:2028–2040. doi: 10.1021/bi00460a011. [DOI] [PubMed] [Google Scholar]
  • 17.Yang SC, Zhu JB. Preparation and characterization of camptothecin solid lipid nanoparticles. Drug Dev Ind Pharm. 2002;28:265–274. doi: 10.1081/DDC-120002842. [DOI] [PubMed] [Google Scholar]
  • 18.Freitas C, Muller RH. Correlation between long-term stability of solid lipid nanoparticles (SLNTM) and crystallinity of the lipid phase. Eur J Pharm Biopharm. 1999;47:125–132. doi: 10.1016/S0939-6411(98)00074-5. [DOI] [PubMed] [Google Scholar]
  • 19.zur Muhlen A, Schwarz C, Mehenert W. Solid lipid nanoparticles (SLN) for controlled drug delivery—drug release and release mechanisms. Eur J Pharm Biopharm. 1998;45:149–155. doi: 10.1016/S0939-6411(97)00150-1. [DOI] [PubMed] [Google Scholar]
  • 20.Jenning V, Thunemann AF, Gohla SH. Characterization of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. Int J Pharm. 2000;199:167–177. doi: 10.1016/S0378-5173(00)00378-1. [DOI] [PubMed] [Google Scholar]
  • 21.Jesser WA, Shneck RZ, Gile WW. Solid-liquid equilibria in nanoparticles of Pb−Bi alloys. Phys Rev B. 2004;69:1–13. doi: 10.1103/PhysRevB.69.144121. [DOI] [Google Scholar]
  • 22.Cavalli R, Aquilano D, Carrlotti ME, Gasco MR. Study by x-ray powder diffraction and differential scanning calorimetry of two model drugs, phenothiazine and nifedipine, incorporated into lipid nanoparticles. Eur J Pharm Biopharm. 1995;41:329–333. [Google Scholar]
  • 23.Cavalli R, Caputo O, Carlotti ME, Trotta M, Scarnecchia C, Gasco MR. Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles. Int J Pharm. 1997;148:47–54. doi: 10.1016/S0378-5173(96)04822-3. [DOI] [Google Scholar]
  • 24.Norris DA, Puri N, Sinko PJ. The effect of physical barriers and properties on the oral absorption of particulates. Adv Drug Deliv Rev. 1998;34:135–154. doi: 10.1016/S0169-409X(98)00037-4. [DOI] [PubMed] [Google Scholar]
  • 25.Andrianov AK, Payne LG. Polymeric carriers for oral uptake of microparticulates. Adv Drug Deliv Rev. 1998;34:155–170. doi: 10.1016/S0169-409X(98)00038-6. [DOI] [PubMed] [Google Scholar]
  • 26.Swartz MA. The physiology of the lymphatic system. Adv Drug Deliv Rev. 2001;50:3–20. doi: 10.1016/S0169-409X(01)00150-8. [DOI] [PubMed] [Google Scholar]
  • 27.Florence AT, Hillery AM, Hussain N, Jani PU. Nanoparticles as carriers for oral peptide absorption: studies on particle uptake and fate. J Control Release. 1995;36:39–46. doi: 10.1016/0168-3659(95)00059-H. [DOI] [Google Scholar]
  • 28.Kreuter J. Peroral administration of nanoparticles. Adv Drug Deliv Rev. 1991;7:71–86. doi: 10.1016/0169-409X(91)90048-H. [DOI] [Google Scholar]
  • 29.Florence AT, Hillery M, Jani PU. Factors affecting the oral uptake and translocation of polystyrene nanoparticles: histological and analytical evidence. J Drug Target. 1995;3:65–70. doi: 10.3109/10611869509015936. [DOI] [PubMed] [Google Scholar]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists

RESOURCES