Synthesis of cholic acid-terminated dendritic lysine block - poly(ethylene glycol)-block - dendritic lysine for paclitaxel delivery

• Main Author: Alba, Laurenzo De Vera
• Format: text
• Language: English
• Published: Animo Repository 2014
• Online Access: https://animorepository.dlsu.edu.ph/etd_masteral/4628
• Institution: De La Salle University

Paclitaxel, a chemotherapeutic drug used to inhibit mitosis in cancer cells, requires the use of the solubilizer Cremophor EL due to its poor water solubility. However, Cremophor EL is associated with adverse reactions following chemotherapy. This study aimed to synthesize an alternative solubilizing agent for use with paclitaxel and similar drugs. Two generations of dendritic lysine were coupled onto both ends of PEG-4000 via reaction of fluorenylmethyloxycarbonyl (FMOC)-lysine-FMOC-OH with dicyclohexylcarbodiimide (DCC)-mediated condensation, and deprotection with 30% piperidine. Cholic acid was attached to the terminal amino groups through the use of DCC/n-hydroxysuccinimide. Synthesis steps were monitored and confirmed by electrospray ionization mass spectroscopy. Paclitaxel loading was induced via the solvent evaporation method. The paclitaxel loading capacity of the synthesized polymer was analyzed by high-performance liquid chromatography. In vitro cytotoxicity assays of the paclitaxel-loaded polymer and polymer alone as compared to commercial paclitaxel formulation were performed on human breast adenocarcinoma (MCF-7) cell line. Masses corresponding to completely-synthesized dendritic polymers were found in the mass spectra. The polymer was able to load up to 47.70% of its mass in paclitaxel. The IC50 values (in 痢/痞) of the paclitaxel-loaded and unloaded polymer were 26.22 and 50.62, respectively. The results suggest that the synthesized polymer is a viable solubilizing agent for delivery of paclitaxel. Additional studies are required to assess its safety and stability.