title: Atrial natriuretic peptide-conjugated chitosan-hydrazone-mPEG copolymer nanoparticles as pH-responsive carriers for intracellular delivery of prednisone.
abstract: A chitosan-hydrazone-mPEG (CH-Hz-mPEG) copolymer which is stable at extracellular pH and cleaves at slightly acidic intracellular pH was synthesized and characterized. Blank polymeric nanoparticles (B-PNPs) and prednisone-loaded polymeric nanoparticles (P-PNPs) were then formulated by dialysis/precipitation method. The cell-specific ligand, atrial natriuretic peptide (ANP) was then conjugated to P-PNPs (ANP-P-PNPs) by a coupling reaction. Particle size and morphological analyses revealed uniform spherical shape of PNPs. In vitro pH dependent degradation of PNPs was investigated. Drug release profile of ANP-P-PNPs indicated a slow release of prednisone at pH 7.4, but a rapid release at pH 5.0 due to the cleavage of hydrazone linkage. Cytotoxicity studies demonstrated greater compatibility of B-PNPs compared to ANP-P-PNPs. Cellular internalization of ANP-P-PNPs was higher than P-PNPs owing to receptor-mediated endocytosis. The results from this investigation support the hypothesis that chitosan based ANP-P-PNPs could act as an intracellular pH-responsive and targeted drug delivery system.
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
authors.forename: Gover Antoniraj
authors.initials: GA
authors.lastname: M
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
authors.forename: Senthil Kumar
authors.initials: SK
authors.lastname: C
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India; National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries (NFDD), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
authors.forename: Linda Jeeva Kumari
authors.initials: LJK
authors.lastname: Henry
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India; National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries (NFDD), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Natesan
authors.affiliation: Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India; National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries (NFDD), Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India. Electronic address: hodpharma@gmail.com.
authors.forename: Ruckmani
authors.initials: R
authors.lastname: Kandasamy
mesh_terms: D000072283:A549 Cells; D009320:Atrial Natriuretic Factor / Q000737:chemistry*; D048271:Chitosan; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D006835:Hydrazones; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D011108:Polymers; D011241:Prednisone / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D006835:Hydrazones; D011108:Polymers; D009320:Atrial Natriuretic Factor; D048271:Chitosan; D011241:Prednisone
keywords: Atrial natriuretic peptide (ANP); Chitosan; Conjugated polymers; Copolymer nanoparticles; Stimuli-sensitive polymers; Targeted drug delivery