Development and In-Vitro Evaluation of Long Circulating Liposomes for Targeted Delivery of Gemcitabine and Irinotecan in Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is a solid malignancy which is one of the leading cause of cancer related deaths in the United States of America. While recent therapeutic advances for patients with advanced pancreatic cancer have shown some potential, but prognosis remains grim with the 5-year survival is much less than 10%, and extremely rare cases of complete remission. The extensive non-targeted treatment approach to pancreatic cancer has a dual drawback of suboptimal drug accumulation at the target site, and the systemic side effects produced by the unfettered exposure of the drug to the healthy tissue. With increasing incidences of drug resistant pancreatic cancer, targeted delivery of the drug to the tumor is the need of the hour. Of all the various approaches, liposomal delivery has emerged as a prime candidate. While surface modification with polyethylene glycol (PEG) conjugates remains the most commonly used technique to develop long circulating liposomes, its shortcomings including but not limited to anaphylatoxin production, platelet activation, immunogenicity, express a need for a better candidate for the same. This article explores the viability of poly(2-ethyl-2-oxazoline) conjugate for the development of long circulating liposomes for the delivery of gemcitabine and irinotecan hydrochloride in pancreatic cancer.|A simple HPLC method was developed for simultaneous quantification of gemcitabine and irinotecan in aqueous medium. The accuracy (% error < 10%) and precision (% RSD < 5%) of the methods followed USP guidelines for validation of an assay method. The liposomes were prepared by hydrating a film of Soy PC and cholesterol with an aqueous hydrating medium comprising of HEPES, Tween 80, and sodium chloride. This dispersion was subjected to freeze thawing and subsequent membrane extrusion. The liposomes were surface modified by incubating the liposomes with 5 mol% of PEG or poly(2-ethyl-2-oxazoline) conjugate and dialyzed against 5% glucose for 12 hours. The study found that the liposomes subjected to surface modification by poly(2-ethyl-2-oxazoline)-cholesterol showed higher macrophagial evasion in comparison to PEGylated liposomes. The liposomal combination therapy of gemcitabine and irinotecan was found to be more efficacious against the pancreatic cancer cell line in comparison to the free drug combination.|Keywords: Pancreatic cancer, long circulating liposome, Polyethylene glycol, Polyoxazoline, Gemcitabine, Irinotecan hydrochloride.
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