Synthesis and Characterization of Sorafenib- and Bosutinib-Encapsulated mPEG-PLGA NPs for the Purpose of Cancer Drug Delivery
Authors:Kinjal Ahir, Carolyn Kan
- Yong Ba, Professor of Chemistry , California State University, Los Angeles
- Jun Wu, Assistant Research Scientist , City of Hope
mPEG-PLGA (methoxy poly(ethylene glycol)- poly(lactic-co-glycolic acid) is an amphiphilic biocompatible polymer which can form nano-scale micelles, or nanoparticles (NPs), in aqueous environment. Hence, hydrophobic drugs are readily encapsulated within the hydrophobic cores of the NPs. In cancer therapies, NPs are found to passively accumulate at solid tumor sites by the enhanced permeability and retention (EPR) effect. This is because angiogenesis generates vessels with fenestrations of 600-800 nm in diameter, and tumors also have an impaired drainage system. Therefore, NPs are promising for targeted delivery of potent hydrophobic anticancer drugs. Two hydrophobic drugs Sorafenib and Bosutinib were chosen for this study. They are kinase inhibitors which have effective binding propensities and are very selective. Sorafenib is used in treating renal carcinoma, while Bosutinib is for chronic leukemia. The objective is to find the experimental methods and conditions to encapsulate these drugs in mPEG-PLGA NPs of the right size. Briefly, the drug loadings and size of the NPs were controlled by finding the content and ratio of the organic and aqueous solvents for making single emulsion mixtures. The drug loading levels and particle sizes were studied by using UV-Vis spectrometry and dynamic light scattering, respectively. The drug release profiles were performed using a PBS-octanol extraction method to collect the drug released from the NPs. Our studies show that under the current conditions Sorafenib and Bosutinib are suitable for NP drug delivery. A higher organic-to-aqueous ratio for the single emulsion method is shown to result in smaller nanoparticles. Additionally, the drug-encapsulated NPs fall within the general drug release kinetics. These results indicate that this method is promising in achieving preferred drug loading levels. The drug delivery efficacies of these nanoparticles will be further tested in mouse models.