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.