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A novel size-tunable nanocarrier system for targeted anticancer drug delivery.


ABSTRACT: We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug-loading capacity. High level of hydrophobic anticancer drugs such as PTX, etoposide and SN-38 can be readily loaded into such nanocarriers. The loading capacity of the nanocarrier for PTX (PTX) is extremely high (12.0mg/mL), which is equivalent to 37.5% (w/w) of the total mass of the micelle. PTX-loaded nanocarriers are much more stable than Abraxane (PTX/human serum albumin nanoaggregate) when stored in bovine serum albumin solution or dog plasma. PTX release profile from the micelles is burst-free and sustained over a period of seven days. The anti-tumor activity of PTX-loaded nanocarriers against ovarian cancer cell line in vitro, with continuous drug exposure, is similar to Taxol (formulation of PTX dissolved in Cremophor EL and ethanol) or Abraxane. Targeted drug delivery to tumor site with these novel micelles was demonstrated by near infrared fluorescence (NIRF) imaging in nude mice bearing ovarian cancer xenograft. Furthermore, PTX-loaded nanocarriers demonstrated superior anti-tumor efficacy compared to Taxol at equivalent PTX dose in ovarian cancer xenograft model.

SUBMITTER: Li Y 

PROVIDER: S-EPMC2878919 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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A novel size-tunable nanocarrier system for targeted anticancer drug delivery.

Li Yuanpei Y   Xiao Kai K   Luo Juntao J   Lee Joyce J   Pan Shirong S   Lam Kit S KS  

Journal of controlled release : official journal of the Controlled Release Society 20100306 3


We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug-loading capacity. High level of hydrophobic  ...[more]

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