fulltext.study @t Gmail

The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs

Paper ID Volume ID Publish Year Pages File Format Full-Text
7175 537 2012 8 PDF Available
Title
The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs
Abstract

A series of biodegradable amphiphilic block copolymers with controlled composition and relatively low polydispersity index were synthesized from monomethoxy polyethylene glycol (mPEG-OH, 5 kDa) via organocatalytic ring opening polymerization of aliphatic cyclic carbonate monomers - trimethylene carbonate (TMC) or cholesteryl 2-(5-methyl-2-oxo-1,3-dioxane-5-carboxyloyloxy)ethyl carbamate (MTC-Chol) or a copolymer of both the monomers (TMC and MTC-Chol): mPEG113-b-PTMC67, mPEG113-b-P(MTC-Chol11) and mPEG113-b-P(MTC-Cholx-co-TMCy)x+y. These well-defined polymers were employed to study the role of molecular weight and composition of the hydrophobic block of the polymers in loading paclitaxel (PTX), an extremely hydrophobic anticancer drug with rigid structure and strong tendency of self-association to form long fibers. The PTX-loaded micelles were fabricated by simple self-assembly without sonication or homogenization procedures. The results demonstrated that the presence of both MTC-Chol and TMC in the hydrophobic block significantly increased PTX loading levels, and the micelles formed from the polymer with the optimized composition (i.e. mPEG113-b-P(MTC-Chol11-co-TMC30)) were in nanosize (36 nm) with narrow size distribution (PDI: 0.07) and high PTX loading capacity (15 wt.%). In vitro treatment of human liver hepatocellular carcinoma HepG2 cells with blank micelles showed that these polymeric carriers were non-cytotoxic with cell viability greater than 90% at ∼2400 mg/L. Importantly, PTX-loaded micelles were able to kill cancer cells much more effectively compared to free PTX. In addition, these nanocarriers also possessed exceptional kinetic stability. The results from non-invasive near-infrared fluorescence (NIRF) imaging studies showed that these micelles allowed effective passive targeting, and were preferably accumulated in tumor tissue with limited distribution to healthy organs.

Keywords
Cholesterol; Polycarbonate; Amphiphilic block copolymer; Micelles; Paclitaxel; Tumor targeting
First Page Preview
The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 6, February 2012, Pages 1921–1928
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering