title: Bombesin-conjugated nanoparticles improve the cytotoxic efficacy of docetaxel against gastrin-releasing but androgen-independent prostate cancer.
abstract: OBJECTIVE
  Bombesin (BBN)-conjugated polymeric nanoparticles to target docetaxel (DTX) to prostate cancer cells that overexpress gastrin-releasing peptides receptors.
  
  
  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.
  
  
  CONCLUSIONS
  This study provides an alternate approach for polysorbate-free delivery of DTX, with improved in vivo performance.
authors.affiliation: IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.|Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.|Health Innovations Research Institute, RMIT University, PO Box 71, Bundoora, Melbourne, VIC 3083, Australia.|School of Applied Sciences, RMIT University, Melbourne, Australia.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Kulhari
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Deep
authors.initials: D
authors.lastname: Pooja
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Mayank K
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.affiliation: Health Innovations Research Institute, RMIT University, PO Box 71, Bundoora, Melbourne, VIC 3083, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001839:Bombesin / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D005755:Gastrins; D043823:Taxoids; D000077143:Docetaxel; D001839:Bombesin
keywords: bombesin; cytotoxicity; docetaxel; nanoparticles; pharmacokinetics; prostate cancer