title: Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel.
abstract: The aim of this research work was to develop Bombesin peptide (BBN) conjugated, docetaxel loaded nanocarrier for the treatment of breast cancer. Docetaxel loaded nanoparticles (DNP) were prepared by solvent evaporation method using sodium cholate as surfactant. BBN was conjugated to DNP surface through covalent bonding. Both DNP and BBN conjugated DNP (BDNP) were characterized by various techniques such as dynamic light scattering, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis. The particle diameter and zeta potential of BDNP were 136±3.95 nm and -10.8±2.7 mV, respectively. The change in surface charge and FTIR studies confirmed the formation of amide linkage between BBN and DNP. AFM analysis showed that nanoparticles were spherical in shapes. In nanoparticles, docetaxel was present in its amorphous form as confirmed by DSC and PXRD analysis and was stable during the thermal studies. The formulations showed the sustained release of DTX over the period of 120 h. During cellular toxicity assay in gastrin releasing peptide receptor positive breast cancer cells (MDA-MB-231), BDNP were found to be 12 times more toxic than pure DTX and Taxotere. The IC50 value for DTX, Taxotere, DNP and BDNP was >375, >375, 142.23 and 35.53 ng/ml, respectively. The above studies showed that Bombesin conjugated nanocarrier system could be a promising carrier for active targeting of anticancer drugs in GRP receptor over expressing cancer cells.
authors.affiliation: IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, India; Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Kulhari
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Deep
authors.initials: D
authors.lastname: Pooja
authors.affiliation: National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Shrivastava
authors.affiliation: National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: Naidu
authors.initials: N
authors.lastname: V G M
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India. Electronic address: sistla@iict.res.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D001839:Bombesin / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D043823:Taxoids / Q000494:pharmacology*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001839:Bombesin
keywords: Bombesin; Breast cancer; Conjugation; Docetaxel; Nanoparticles; Targeting