Mahua Sarkar, PhD, Formulation Research Scientist
TSU Mentor: Huan Xie, PhD, Professor in Pharmaceutics
External Mentor: Diana Chow, PhD (University of Houston)
Project Title: Development and Evaluation of Giα2 Inhibitor Formulations for Treatment of CRPC
Project Summary:
前列腺癌(PCa)是美国男性癌症死亡的第二大原因,常见于65岁以上的男性和非洲裔. The number of new cases diagnosed in African American men is nearly 80% higher than the number of new cases diagnosed in white men. For advanced PCa, androgen deprivation therapy (ADT) is the primary standard of care. Despite initial positive responses to drugs like Enzulatamide and Bicalutamide, treatment failure occurs in 15-25% of patients and develop metastatic castration-resistant prostate cancer (mCRPC). Currently, very limited therapeutic options are available for CRPC, however, the success of treatment is modest. 通过计算对接分析,我们确定了Giα2的小分子抑制剂,并合成了两类不同的抑制剂, Dr. Oyelere’s lab at Georgia Tech University. Class I and Class II molecules are Phenolic ketimine (compounds 7,8), Phenoxyethyl-1H-indole (compounds 13,14), respectively. In vitro cell migration assays in prostate cancer cell lines demonstrated significant, dose-dependent inhibition of migration. 在前列腺癌细胞中有希望的抗肿瘤功效促使我们进一步表征这些化合物的物理化学和药代动力学特性(7),8,13 and 14), investigate their pharmacokinetics and bio specifically deliver the compounds to the tumor site, distribution behavior in rats, and develop novel delivery formulation. It is necessary to formulate an optimum drug delivery system that will ensure higher solubility, bioavailability, specifically deliver the compounds to the tumor site, and steadily release the drug at a controlled rate. Our specific aims are to characterize physicochemical properties of Giα2 inhibitors (solubility, logP, pKa, stability) and develop solution formulations to be used in pharmacokinetic studies; to characterize basic in vivo pharmacokinetic and biodistribution pattern of the compounds; to develop and characterize an optimum nano-formulation (solid lipid nanoparticle) of Giα2 inhibitors. Desired characteristics of optimum nanoformulation are uniform shape, small particle size, low polydispersity index (PDI), and high encapsulation efficiency. This project will seek support and evaluation from the CBMHR Administrative Core and utilize the Research Infrastructure Core to perform experiments. Research findings from this project will be shared with various TSU communities via Community Engagement Core (CEC). The successful execution of this research will result in potential advanced treatment for CRPC patients.
Award amount: $49,650 (direct cost)