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

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 (12.0 mg/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.