Controlled Delivery of Salmon Calcitonin Using Thermosensitive Triblock Copolymer Depot for Treatment of Osteoporosis.

ACS Omega

Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, North Dakota, United States.

Published: January 2019

Osteoporosis is a common metabolic bone disorder associated with fragility and bone fracture. Worldwide, osteoporosis results in more than 8.9 million fractures annually. Additionally, steroid treatments can cause osteoporosis as a side effect. Salmon calcitonin (sCT) is injected daily for those on steroid treatments as a means to prevent and treat osteoporosis side effects. Frequent dosing is inconvenient, uncomfortable, and often leads to compliance issues. Our objective was to develop a monomethoxy poly(ethylene glycol) (mPEG) and poly-lactic--glycolic acid (PLGA) thermosensitive triblock copolymer (mPEG-PLGA-mPEG)-based controlled release delivery system at an increased lactide to glycolide ratio (3.5:1, 4.5:1, and 5:1) to deliver sCT in its active conformation in a controlled fashion for a prolonged period following a single subcutaneous injection. Increasing lactide to glycolide ratio increases hydrophobicity of the PLGA block, which slows degradation of copolymer, thereby prolonging release and reducing burst release. Proton nuclear magnetic resonance spectroscopy and gel permeation chromatography confirmed structural composition and polydispersity index, respectively. Critical micelle concentration of the copolymer was 25 μg/mL. The delivery system was biocompatible as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay. Moreover, the copolymeric system maintained sCT in a conformationally stable form for the entire duration of storage and release.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356892PMC
http://dx.doi.org/10.1021/acsomega.8b02781DOI Listing

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