The effects of the nanosphere carrier for the combined carmustine-busulfan trastuzumab in human breast cancer tissue culture

Abstract

Cancer of the breast is from the highest cancer type's incidence. Cancer in general represents a high therapeutic challenge. Considerable adverse effects and cytotoxicity of highly potent drugs for healthy tissue require the development of novel drug delivery systems to improve pharmacokinetics and result in selective distribution of the loaded agent. Targeted therapy is a novel maneuver to achieve proper selectivity index. And as the main goal of nanocarriers is to target specific sites and improve the circulation time of the drug which is entrapped, encapsulate or conjugate in the carrier system so we chose nanoliposome as a drug carrier. Liposomes improved a potent drug targeting successfully in the last decade, but nanoliposomes offer more surface area and they have more solubility, improve controlled release, enhance bioavailability, and permit precision targeting of the material that is encapsulated to a greater extent. The Aims and objectives of the study is the formulation of HER2 Ab directed nanosphere carrier for a combined Carmustine-busulfan and trastuzumab (LCBT), then Assessing antineoplastic efficacy of (LCBT) in lung carcinoma cell line. A dose-dependent cellular growth inhibition on all three cell lines (P-value < 0.001) was seen. The concentration of 100 µg/ml of LCBT show highly significant inhibitory effect (P-value < 0.001) on cancer cell line in comparison to other concentration and other positive control drugs that forming the combination separately (P-value <0.001). The means of the half-maximal inhibitory concentration (IC50) values for LCBT combination show highly significant difference (P-value < 0.001) from other positive control groups. At the same time, the interaction indexes IAI for LCBT and for LT and LCB separately show synergistic effect that was less than one. The results of the present study also revealed a reduced expression percentages of proliferation marker Ki67 in MCF-7 cancer cell line that was treated with IC50 of LCBT and positive control (LT, LCB, T and CB) after 48 hour from drug exposure in comparison with the negative control group (P-value <0.001). Also, there was a significant decrease in expression percentages in CB containing positive control groups in comparison to T containing positive control (P-value <0.01). From the above results, we conclude that the LCBT has a prominent anticancer effect in MCF-7 breast cancer cell line as it significantly decreased the growth percentage and show apoptotic effects.