FORMULATION AND EVALUATION OF DOCETAXEL TRIHYDRATE LOADED SELF-ASSEMBLED NANOCARRIERS FOR TREATMENT OF HER2 POSITIVE BREAST CANCER

Abstract

Human Epidermal Growth Factor Receptor 2-positive (HER2-positive) breast cancer tend to be more aggressive among all breast cancers. Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive. It tends to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers. HER2 positive breast cancer is often treated with chemotherapy drugs called anthracylines (e.g. doxorubicine, epirubicine), taxanes (e.g. Docetaxel, peclitaxel) as well as some others, usually in combination of two or more chemotherapy drugs1 but the development of potential drug delivery system by using nanotechnology is also the important aspect for the proper treatment of HER2 positive breast cancer. The aim of this study was to develop DTX-loaded self assembled nanocarriers (SANs) for treatment of HER2 positive breast cancer and also to evaluate their efficacy to release the drug by controlled manner. SANs were prepared from a glyceryl monooleate, Pluronic® F127 (0.5 – 1.5 % w/v) and Pluronic® F68 (0.25-1.0 %w/v) in different concentration with or without docetaxel trihydrate (DTX) (2.0%w/v) by high pressure homogenization, before preparation compatibility of drug and polymers was studied by differential scanning calorimetry (DSC) and FTIR spectroscopy. Prepared SANs was then subject to different evaluation test particle size, zeta potential, % entrapment efficiency, drug content, in vitro drug release study, measurement of pH, and stability study. Particle size of SANs prepared with Pluronic® F127 was found in the range of 170 nm to 280 nm whereas SANs with Pluronic® F68 was found between 200 to 240 nm and it shows more negative zeta potential value than -30 mV. More than 90 % of DTX was found to be entrapped in SANs formulations loaded with DTX 2.0% w/v. Drug released study revealed that formulation F9 containing 0.25% PF68 shows 89.59 % release after 12 h and F5 containing 1.0% PF127 releases 96.56% drug after 12 h. Results of one month stability study shows that the SANs formulations were found to be stable over a one month. Hence, the DTX-loaded SANs was act as an potential drug carrier to fulfill the demand of cancer therapeutics.