Preparation, Characterization And In Vitro Evaluation Of Antitumor Activities Of Vinblastine-loaded Folate-conjugated Albumin Nanoparticles

As an important antineoplastic drug in clinical, vinblastine has a better curative effect on Hodgkin’s disease and chorioepithelioma than others. Vinblastine exists in catharanthus roseus and it is formulated in sulfate because of its low solubility, but it still has side-effect, including vomit, neurotrophin, medulla-suppressed and so on. In addition, non-targeted is another shortcoming of vinblastines. It has a good efficacy in antineoplastic while damage in normal tissue. Nano-carrier was used in the preparation of targeting and sustained-release formulations of medicine. It has three effects, including surface-interface, quantum-size and small size effect. Due to the large surface area, small size and high surface energy of nano-carrier, it not only increases the solubility of drugs, but also improves the bioavailability. It takes the initiative to search and attacks tumor cells after enters the body. It provides a new way for researching of nanomedicine.In this study, vinblastine loaded nanoparticles were prepared by desolvation procedure and subsequent cross-linking of the wall material of bovine serum albumin (BSA). Response surface methodology (RSM) based on central composite design (CCD) was utilized to optimize the process of preparing VLB-BSANP. High performance liquid chromatograph, infrared chromatograph and laser particle size analyzer were used to detect physical characterization and stability of VLB-BSANP and FA-VLB-BSANP. MTT assay and confocal laser scanning were used to activity detection in vitro. And the study was carried out using human oophoroma cells (HO-8910), human liver cancer cells (SMMC-7721) and human lung adenocarcinoma cells (A549).In this study:1、The conditions of the preparation of VLB-BSANP were observed that the concentration of BSA is7.75mg/mL, the volume ratio of ethanol and water is4.25, and the theoretical drug loading efficiency is40%.2、The nanoparticles were characterized with a narrow size distribution. It has a high drug loading capacity and entrapment efficiency and the stability is good.3、The drug carrier system had a burst release in13hours and a slow release up to77hours, releasing approximately34%and69%of VLB, respectively.4、The cytotoxicity of FA-VLB-BSANP, VLB-BSANP and vinblastine increase as the dose of drugs increase. The best anti-tumor activity is FA-VLB-BSANP and the most obvious effect is SMMC-7721.5、The targeting of FA-VLB-BSANP is obvious.The results indicated that the FA-VLB-BSANP was characterized with a narrow size distribution and the anti-tumor activity is better than VLB-BSANP. The further study is based on it.