title: Gemcitabine-loaded PLGA-PEG immunonanoparticles for targeted chemotherapy of pancreatic cancer.
abstract: The aim of the present study was the direct covalent coupling of the epidermal growth factor receptor (EGFR)-specific monoclonal antibody (mAb) to the surface of poly(lactide)-co-glycolide (PLGA)-polyethylene glycol (PEG) nanoparticles in order to achieve a cell type-specific drug carrier system against pancreatic cancer. The PLGA-PEG-NH2diblock copolymer was synthesized by coupling reaction via amide linkage between PEG-diamine and activated PLGA. PLGA and PLGA-PEG-NH2nanoparticles loaded with gemcitabine were prepared using the double-emulsion solvent evaporation method. PLGA-PEG immunonanoparticles were prepared by glutaraldehyde mediated cross-linking method. The conjugated antibody was analysed by transmission electron microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) analysis. Cell viability study was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell uptake study was performed on fluorescein isothiocyanate-loaded formulations using confocal microscopy. The PAGE results indicated that mAb integrity was remained intact in the formulations after conjugation. Biological activity was confirmed under cell culture conditions: antibody-conjugated nanoparticles showed specific targeting to EGFR-overexpressing MIA PaCa-2 cell lines as shown in fluorescence image using confocal microscopy. The obtained data provide the basis for the development of stable and biologically active carrier systems for direct targeting of tumour cells using antibody-conjugated PLGA-PEG nanoparticles. Direct covalent coupling of antibodies to nanoparticles using glutaraldehyde as a cross-linker is an appropriate method to achieve cell type-specific drug carrier systems based on PLGA-PEG nanoparticles and the anti-EGFR-decorated PLGA-PEG nanoparticles have potentials to be applied for targeted chemotherapy against EGFR positive cancers.
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga, 142-001 Punjab India.
authors.forename: Sahil
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga, 142-001 Punjab India ; School of Pharmaceutical Sciences, Apeejay Stya University, Sohna-Palwal Road, Sohna-, 122103 Gurgaon (Haryana) India.
authors.forename: Swati
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga, 142-001 Punjab India.
authors.forename: Dilrose
authors.initials: D
authors.lastname: Pabla
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga, 142-001 Punjab India.
authors.forename: R S R
authors.initials: RS
authors.lastname: Murthy
keywords: Adenocarcinoma; Epidermal growth factor receptor; Gemcitabine; MIA PaCa-2; Multifunctional nanoparticles; Targeting