Enhanced Topical Delivery of Cyclosporin-A Using PLGA Nanoparticles as Carrier

Sanyog      Jain; Ankit      Mittal; Amit      K. Jain

doi:10.2174/157341311796196835

Abstract

Cyclosporin-A is a drug of choice for the topical treatment of various dermatological diseases, however the drug failed to penetrate into intact skin barrier due to its high molecular weight, complex cyclic molecular structure and the barrier property of stratum corneum (SC). Less than 1% of the drug reaches skin upon systemic administration and it further causes systemic toxicity. So the aim of the present work was to develop cyclosporine-A loaded PLGA nanoparticles for enhancing its topical delivery. Spherical shaped nanoparticles with high entrapment efficiency (86%), low particle size (163 nm) and narrow polydispersity index (0.118) were prepared by emulsion diffusion evaporation technique. In vitro permeation studies were carried out using rat skin and 6.6 and 4.85 times higher amount of the drug was estimated in SC and dermis respectively as compared to free drug. No drug was detected in receptor compartment hence the system might be devoid of risk of any systemic toxicity. Histological examination and TEWL measurement exhibited no morphological changes upon application of nanoparticles on the skin. CLSM images suggested pilosebaceous route followed by nanoparticles for skin penetration. The system may be a promising carrier for topical delivery of cyclosporin.

Keywords: Cyclosporin A, PLGA nanoparticles, Topical delivery, Skin permeation, CLSM, PLGA, Nanoparticles, pilosebaceous route, tape stripping, TEWL, transfollicular route, AFM, DSC