Hitesh Kulhari1,2,3,4, Deep Pooja2, Mayank K Singh2, Madhusudana Kuncha2, David J Adams3, Ramakrishna Sistla2. 1. IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. 2. Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. 3. Health Innovations Research Institute, RMIT University, PO Box 71, Bundoora, Melbourne, VIC 3083, Australia. 4. School of Applied Sciences, RMIT University, Melbourne, Australia.
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.
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 humanprostate 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.
Entities:
Keywords:
bombesin; cytotoxicity; docetaxel; nanoparticles; pharmacokinetics; prostate cancer
Authors: Terry W Moody; Lingaku Lee; Irene Ramos-Alvarez; Tatiana Iordanskaia; Samuel A Mantey; Robert T Jensen Journal: Front Endocrinol (Lausanne) Date: 2021-09-01 Impact factor: 5.555