title: In vitro and in vivo evaluation of osteoporosis therapeutic peptide PTH 1-34 loaded pegylated chitosan nanoparticles.
abstract: Oral formulation of human parathyroid hormone 1-34 (PTH 1-34) is an alternative patient compliant route in treating osteoporosis. PTH 1-34 loaded chitosan nanoparticles were PEGylated (PEG-CS-PTH NPs) and characterized by DLS, SEM, TEM and FTIR. PEG-CS-PTH NP aggregates of 200-250 nm which in turn comprised 20 nm individual nanoparticles were observed in SEM and TEM images respectively. The PEG-CS-PTH NP with 40% encapsulation efficiency was subjected to an in vitro release in simulated rat body fluids. PEG-CS-PTH NP treated human primary osteoblast cells, upon PTH 1-34 receptor activation, produced second messenger-cAMP, which downstream stimulated intracellular calcium uptake, production of bone specific alkaline phosphatase, osteocalcin etc., which substantiates the anabolic effect of the peptide. PEG-CS-PTH NPs showed an oral bioavailability of 100-160 pg/mL PTH 1-34 throughout 48 h, which is remarkable compared to the bare PTH 1-34 and CS-PTH NPs. The NIR image of gastrointestinal transit of ICG conjugated PEG-CS-PTH NPs supports this significant finding.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University , Kochi-682041, India.
authors.forename: Deepa
authors.initials: D
authors.lastname: Narayanan
authors.forename: A
authors.initials: A
authors.lastname: Anitha
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
authors.forename: K P
authors.initials: KP
authors.lastname: Chennazhi
mesh_terms: D000818:Animals; D002151:Calorimetry; D049109:Cell Proliferation; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D053758:Nanoparticles / Q000737:chemistry*; D010024:Osteoporosis / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats
chemical_list: D010281:Parathyroid Hormone; D011092:Polyethylene Glycols; D048271:Chitosan