Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer. (2nd January 2016)

• Record Type: Journal Article
• Authors: Liang, Su; Bian, Xiaomei; Liang, Dong; Sivils, Jeffrey C.; Neckers, Leonard M.; Cox, Marc B.; Xie, Huan
• Is Part Of: Pharmaceutical development and technology. Volume 21:Number 1(2016)
• Page Start: 121
• Page End: 126
• Publication Date: 2016-01-02
• Subjects: Androgen-independent -- castration-resistant prostate cancer -- efficacy -- formulation -- MJC13 -- preformulation; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.3109/10837450.2014.979946
• Languages: English
• ISSNs: 1083-7450

Abstract

Abstract: MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water (0.28 µg/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls.