Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer
semanticscholar(2021)
摘要
PLGA Poly (lactide-co-Glycolide) is a biocompatible and biodegradable copolymer gained popularity for tissue engineering, drug delivery, biosensing, and biomedical applications. In the present study PLGA of (Mw =13,900) has synthesized by ring opening polymerization with zinc proline initiator. Irinotecan (Ir) loaded Lipomers (LPs) formulated with PLGA, DSPE-PEG (2000) (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000) and soya lecithin excipients by nanoprecipitation method. These formulated LPs further validated by physicochemical and biological potential for colon delivery applications. The potential of LPs for delivery of Irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon cancer was studied. LPs of controlled size (80-120 nm), surface charge (~ -35 mV), sustained release potential and significant cytotoxicity against CT-26 (colon) cancer cells, were successfully prepared. In-vivo biodistribution and tumor site retention in CT-26 xenografts tumor bearing Balb/C mice showed promising result for tumor uptake and retention for prolong time period. Unlike P-DSPE-Ir, PEG coated P-DSPE-PEG-Ir LPs exhibit significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 10 mg Ir/kg dose. The biocompatibility, safety of LPs confirmed by acute toxicity study of optimized formulation. Overall, this proof-of-concept study demonstrates that the LPs improved efficacy, bioavailability and decreases neutropenia of Ir to combat colon cancer.
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关键词
irinotecan loaded lipomers,colon cancer
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