Abstract

PHARMACOLOGICAL DEVELOPMENT AND TRANSLATION OF TARGETED NANOPARTICLES FOR THE TREATMENT OF PROSTATE CANCER

Nouratan Singh*, Dr. Neeraj Tandan, Dr. S.P. Singh and Dr. Dalel Singh

ABSTRACT

The targeted nanoparticle play an important role for the treatment of prostate cancer. The recently we studied the formulation of nanoparticles. We also developed and clinical translate of a polymeric targeted nanoparticle (TNP) which are containing the chemotherapeutic agent in case of the treatment of patients of solid tumors like docetaxel drug (DTXL). DTXL-NP is a combination for targeted to clinically validated tumor antigen expressed on prostate cancer cells prostate-specific membrane antigen (PSMA). The combination of docetaxel drug and targeted-nanoparticle (DTXL-TNP) developed from various particle size in combinatorial library of more than 100 TNP formulations, drug loading, targeting ligand density, surface hydrophilicity and properties of drug releasing. The tissue distribution and pharmacokinetic studies in rats showed minimal liver accumulation and blood circulation half-life of about 22 hours. In mice, targeted combination of DTXL-TNP exhibited markedly likely more suitable for tumor accumulation at 12 hours and extended for tumor growth suppression compared to formulation of a solvent-based docetaxel drug. In mice (tumor-bearing), rats, DTXL-TNP displayed pharmacokinetic characteristics constant with extended circulation of nanoparticles in the vascular compartment and controlled releasing of DTXL with total DTXL plasma concentrations finally at least 100-fold higher than solvent-based DTXL for slightly more than 24 hours. Finally, preliminary clinical data indicated that DTXL-TNP displays a profile of pharmacological differentiated from solvent-based DTXL, together with pharmacokinetics characteristics constant with preclinical data in patients with advanced solid tumors and cases of tumor shrinkage at doses under the solvent-based DTXL dose in case of treatment.

Keywords: Targeted Nanoparticle, PSMA, chemotherapeutic docetaxel, Prostate, liver accumulation.