Bombesin-conjugated nanoparticles improve the cytotoxic efficacy of docetaxel against gastrin-releasing but androgen-independent prostate cancer.

Abstract

AIM:

Bombesin (BBN)-conjugated polymeric nanoparticles to target docetaxel (DTX) to prostate cancer cells that overexpress gastrin-releasing peptides receptors.

MATERIALS & METHODS:

In vitro cytotoxicity, uptake of nanoparticles and inhibition of cell migration were assessed against human prostate cancer cells. Preclinical pharmacokinetic and tissue-distribution studies of nanoparticles were performed in Balb/c mice and results compared with the marketed formulation Taxotere(®).

RESULTS:

BBN-conjugated DTX-loaded nanoparticles exhibited higher cytotoxicity, inhibition of cell migration and colony formation than non-targeted nanoparticles or DTX alone. More BBN-conjugated nanoparticles were taken up at a faster rate than unconjugated nanoparticles. In vivo, this drug delivery improved pharmacokinetics of DTX by increasing mean residence time and decreasing clearance.

CONCLUSION:

This study provides an alternate approach for polysorbate-free delivery of DTX, with improved in vivo performance.

• Authors: Hitesh Kulhari, Deep Pooja, Mayank K Singh, Madhusudana Kuncha, David J Adams, Ramakrishna Sistla
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 10 Issue 18 Pg. 2847-59 ( 2015) ISSN: 1748-6963 [Electronic] England
• PMID: 26377157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Antineoplastic Agents
• Gastrins
• Taxoids
• Docetaxel
• Bombesin

Topics

• Androgens (metabolism)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Bombesin (analogs & derivatives)
• Cell Line, Tumor
• Docetaxel
• Drug Delivery Systems
• Gastrins (metabolism)
• Humans
• Male
• Mice, Inbred BALB C
• Nanoparticles (chemistry)
• Prostate (drug effects, metabolism, pathology)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Taxoids (administration & dosage, pharmacokinetics, therapeutic use)