Bioequivalence Study of Pegylated Doxorubicin Hydrochloride Liposome (PEGADRIA) and DOXILÃÂ® in Ovarian Cancer Patients: Physicochemical Characterization and Pre-clinical StudiesAli SM1, Sheikh S1, Ahmad A1, Ahmad MU1, Chen P2, Paithankar M3, Choudhury K4, Makadia RD5, Kumar A6, Velavan K7, Satheesh CT8, Singh JK9, Mamillapalli G10, Saptarishi D3, Kale P11, Patel R11, Barkate HV3 and Ahmad I1*
- *Corresponding Author:
- Imran Ahmad
Jina Pharmaceuticals Inc 28100
Ashley Circle, Suite 103
Libertyville, IL 60048, USA
E-mail: [email protected]
Received Date: March 02, 2016; Accepted Date: March 16, 2016; Published Date: March 23, 2016
Citation: Ali SM, Sheikh S, Ahmad A, Ahmad MU, Chen P, et al. (2016) Bioequivalence Study of Pegylated Doxorubicin Hydrochloride Liposome (PEGADRIA) and DOXIL® in Ovarian Cancer Patients: Physicochemical Characterization and Pre-clinical studies. J Nanomed Nanotechnol 7: 361. doi:10.4172/2157-7439.1000361
Copyright: © 2016 Ali SM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective:To develop Pegylated Doxorubicin Hydrochloride Liposome (PEGADRIA) and compare its physicochemical properties, preclinical safety and efficacy, clinical pharmacokinetic and safety profiles with those of the reference product, Doxil®.
Methods: PEGADRIA was prepared and the structure morphology, lamellarity, size, shape, drug loading, lipid bilayer and Peg layer thickness were determined. Safety studies were conducted in mice and rats and efficacy study was conducted in a P-388 leukemia mouse model. To evaluate the pharmacokinetic profile of PEGADRIA, a multicenter, open label, balanced, randomized, two-treatment, two-period, two-sequence, single dose cross-over bioequivalence study was conducted with Doxil® in ovarian cancer patients whose disease had progressed or reoccurred after platinum based chemotherapy under fasting conditions. The pharmacokinetic parameters were determined based on the concentration-time profiles of doxorubicin, whereas the concentration was determines using LC-MS/MS methods.
Results: PEGADRIA was similar to Doxil® in terms of general morphology, lamellarity, size, shape, drug loading, lipid bilayer and Peg layer thickness. PEGADRIA and Doxil® showed comparable survival benefit in leukemic mice. The toxicity profiles of PEGADRIA in both mice and rats were comparable to those of Doxil®. Plasma concentrations of doxorubicin from cancer patients were measured to determine the pharmacokinetics profile. The geometric mean ratios (90% confidence intervals) of PEGADRIA /Doxil® for free doxorubicin and encapsulated doxorubicin were similar.
Conclusion: PEGADRIA was found to have similar physicochemical profile compared to Doxil®. In addition, it was safe and bioequivalent to Doxil® in ovarian cancer patients.