Prodrug based nano drug delivery system for co encapsulate paclitaxel and carboplatin for lung cancer treatment
Abstract Context: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non small cell lung cancer (NSCLC) However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non tumor areas are major obstacles to the success of chemotherapy in treating cancers. Objective: This study aimed to engineer a prodrug based nano drug delivery system for co encapsulate hydrophilic (CBP) and hydrophobic anti tumor drugs (PTX) This system was expected to resolve the multidrug resistance cause by single drug, and the dual drug loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. Methods: In this paper, PLGA PEG CBP was synthesized by the conjugation between the carboxylic group of PLGA PEG COOH and the amino group of CBP. Then, self assembled nanoparticles for combination delivery of PTX and PLGA PEG CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti tumor efficacy was assessed in NCL H460 human non small cell lung carcinoma cell line. Results: PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co delivery of PTX and CBP possessed high tumor targeting capacity and strong anti tumor activity. Conclusions: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.
Drug delivery