PTH 1-34 Loaded Thiolated Chitosan Nanoparticles for Osteoporosis: Oral Bioavailability and Anabolic Effect on Primary Osteoblast Cells
In this work, biocompatible and mucoadhesive thiolated chitosan (TCS) was used in the preparation of oral nanoformulation of human parathyroid hormone 1-34 (PTH 1-34) as an alternative patient compliant route in treating osteoporosis. PTH 1-34 loaded thiolated chitosan nanoparticles (TCS-PTH 1-34 NPs) size, morphology and interaction was analysed by DLS, SEM and FTIR respectively. TCS-PTH 1-34 NPs (90–100 nm) with 60% encapsulation efficiency was subjected to an in vitro release in simulated rat body fluids. TCS-PTH 1-34 NP's treated human primary osteoblast cells (HOB) upon PTH 1-34 receptor activation, produced second messenger-cAMP which down stream stimulated, production of bone specific alkaline phosphatase, osteocalcin and even enhanced the intracellular calcium uptake. These data substantiates the anabolic effect and bioactivity of the PTH 1-34 released from the TCS-PTH 1-34 NPs. Bare PTH 1-34 failed to reach the systemic circulation following oral dosage in rats whereas TCS-PTH 1-34 NPs showed an oral bioavailability of 0.075 μg PTH 1-34 throughout 48 h which is indeed a significant improvement in the half life of this peptide. TSC-PTH 1-34 NPs have released an advantageous anabolic dose of the peptide in blood that is suited for the treatment of osteoporosis. NIR image of gastrointestinal transit of ICG conjugated nanoformulation supports and justifies this significant finding. These results cumulatively point out that TCS NPs loaded with PTH 1-34 is efficient in orally delivering the peptide. This route of administration has increased its half life and improved the bioavailability compared to the bare peptide that is delivered systemically for treating osteoporosis.
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Document Type: Research Article
Publication date: January 1, 2014
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