title: Development of amphotericin B loaded polymersomes based on (PEG)(3)-PLA co-polymers: Factors affecting size and in vitro evaluation.
abstract: Amphotericin B (AmB) is a broad spectrum antifungal and antileishmenial agent and its clinical use is limited due to substantial dose limiting toxicities such as nephrotoxicity. In this work, amphotericin B is formulated in polymersomes of branched (PEG)(3)-PLA co-polymer. Polymersomes were prepared by solvent injection method and the effects of various formulation and process parameters on size and size distribution were studied. The results showed that viscosity of biphasic solution during formulation has significant influence on the size and size distribution of the polymersomes. Further, drug-loaded polymersomes with size of 199.6+/-14.1nm, PDI of 0.258+/-0.18, zeta potential (zeta) of -18.07+/-4.91mV and loading of 16.26+/-2.50% were obtained. Drug was found to be intercalated in the wall of polymersomes as observed using FITC tagged drug and CLSM study. An in vitro release media containing sodium deoxycholate was developed and a significant amount of drug release was observed up to 24h there after a very slow release was obtained. Free drug was not found in the formulation and different molecular forms of the drug (AmB) were observed by UV-visible spectroscopy and circular dichroism. This was further supported by hemolysis experiments, where negligible hemolysis in the test formulation was observed as compared to 100% hemolysis in a marketed formulation (Fungizone).
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research, S.A.S. Nagar, India.
authors.forename: Jay Prakash
authors.initials: JP
authors.lastname: Jain
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000666:Amphotericin B / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D000935:Antifungal Agents / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate; D006461:Hemolysis / Q000187:drug effects; D019344:Lactic Acid / Q000032:analysis / Q000737:chemistry; D008297:Male; D008863:Microspheres; D036103:Nanotechnology; D010316:Particle Size; D011100:Polyglycolic Acid / Q000032:analysis / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D013501:Surface-Active Agents; D013678:Technology, Pharmaceutical
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D011108:Polymers; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B; D016650:Fluorescein-5-isothiocyanate