Biodistribution of Fracture-Targeted GSK3β Inhibitor-Loaded Micelles for Improved Fracture Healing

Biomacromolecules
Stewart A LowJindřich Kopeček

Abstract

Bone fractures constitute a major cause of morbidity and mortality especially in the elderly. Complications associated with osteoporosis drugs and the age of the patient slow bone turnover and render such fractures difficult to heal. Increasing the speed of fracture repair by administration of a fracture-targeted bone anabolic agent could find considerable application. Aspartic acid oligopeptides are negatively charged molecules at physiological pH that adsorb to hydroxyapatite, the mineral portion of bone. This general adsorption is the strongest where bone turnover is highest or where hydroxyapatite is freshly exposed. Importantly, both of these conditions are prominent at fracture sites. GSK3β inhibitors are potent anabolic agents that can promote tissue repair when concentrated in a damaged tissue. Unfortunately, they can also cause significant toxicity when administered systemically and are furthermore difficult to deliver due to their strong hydrophobicity. In this paper, we solve both problems by conjugating the hydrophobic GSK3β inhibitor to a hydrophilic aspartic acid octapeptide using a hydrolyzable bond, thereby generating a bone fracture-targeted water-soluble form of the drug. The resulting amphiphile is shown to a...Continue Reading

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Citations

Jun 9, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Libin ZhangJindřich Kopeček
Aug 30, 2020·Current Osteoporosis Reports·Jeffery J Nielsen, Stewart A Low
Aug 10, 2016·Current Osteoporosis Reports·T A Asafo-AdjeiD A Puleo
Dec 22, 2020·Medicinal Research Reviews·Farideh OrdikhaniNasim Annabi
Oct 9, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jeffery J NielsenPhilip S Low
Feb 23, 2018·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Yuchen WangDanielle S W Benoit
Jul 29, 2021·Journal of Biomedical Materials Research. Part a·Marian A Ackun-FarmmerDanielle S W Benoit
Jun 26, 2018·ACS Applied Materials & Interfaces·Qingchang ChenWilliam W Lu
Aug 31, 2021·Current Opinion in Biomedical Engineering·Marian A Ackun-FarmmerDanielle S W Benoit

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