Novel genipin crosslinked atorvastatin loaded sericin nanoparticles for their enhanced antihyperlipidemic activity.
The objective of this study was to demonstrate the therapeutic as well as biopolymer like characteristics of naturally occurring sericin protein for development of nanoparticulate system of atorvastatin (Atr) to improve therapeutic effect and to reduce toxicity. The sericin encapsulated atorvastatin nanoparticles (Seri-Atr NPs) were prepared by desolvation method utilizing genipin (Gn) as a natural and nontoxic crosslinker. The optimized NPs exhibited small particle size (166±0.30nm), high entrapment efficiency (91±0.69%) and uniform spherical shape with sustained release profile. Moreover, the results of pharmacokinetic studies indicated an increase in AUC0-∞ of NPs (1189.74±52.3hng/ml) compared with Atr (501.84±66hng/ml). The cellular uptake of NPs suggested an interaction of negatively charged particles with the cell surface and considerable reduction in systemic toxicity. Histopathology studies also demonstrated the therapeutic potential of sericin and cytocompatibility. Hence, genipin crosslinked sericin based nanoparticles represents a promising nanoplatform for improved therapeutic efficiency of Atr.
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P. 226025, India.
Jovita
J
Kanoujia
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P. 226025, India.
Mahendra
M
Singh
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P. 226025, India.
Pooja
P
Singh
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P. 226025, India. Electronic address: shubhini.saraf@gmail.com.
Shubhini A
SA
Saraf
D000818:Animals; D000069059:Atorvastatin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D012831:Bombyx; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases; D000960:Hypolipidemic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D039823:Iridoids / Q000737:chemistry*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D047030:Sericins / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014961:X-Ray Diffraction
D000960:Hypolipidemic Agents; D039823:Iridoids; D008055:Lipids; D047030:Sericins; D000069059:Atorvastatin; C007834:genipin; D006903:Hydroxymethylglutaryl CoA Reductases
Antihyperlipidemic activity; Crosslinking; Desolvation; Genipin; Nanoparticles; Sericin