AUTHOR=Que Yunduan , Yang Yuhang , Zafar Hajra , Wang Dongming 

TITLE=Tetracycline-grafted mPEG-PLGA micelles for bone-targeting and osteoporotic improvement

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.993095

DOI=10.3389/fphar.2022.993095

ISSN=1663-9812

ABSTRACT=<p><bold>Aim:</bold> We aimed to create a nano drug delivery system with tetracycline (TC)-grafted methoxy poly-(ethylene-glycol)‒poly-(D, L-lactic-co-glycolic acid) (mPEG‒PLGA) micelles (TC‒mPEG‒PLGA) with TC and mPEG‒PLGA for potential bone targeting. Prospectively, TC‒mPEG‒PLGA aims to deliver bioactive compounds, such as astragaloside IV (AS), for osteoporotic therapy.</p><p><bold>Methods:</bold> Preparation and evaluation of TC‒mPEG‒PLGA were accomplished via nano-properties, cytotoxicity, uptake by MC3T3-E1 cells, ability of hydroxyapatite targeting and potential bone targeting <italic>in vivo,</italic> as well as pharmacodynamics in a rat model.</p><p><bold>Results:</bold> The measured particle size of AS-loaded TC‒mPEG‒PLGA micelles was an average of 52.16 ± 2.44 nm, which exhibited a sustained release effect compared to that by free AS. The TC‒mPEG‒PLGA demonstrated low cytotoxicity and was easily taken by MC3T3-E1 cells. Through assaying of bone targeting <italic>in vitro</italic> and <italic>in vivo</italic>, we observed that TC‒mPEG‒PLGA could effectively increase AS accumulation in bone. A pharmacodynamics study in mice suggested potentially increased bone mineral density by AS-loaded TC‒mPEG‒PLGA in ovariectomized rats compared to that by free AS.</p><p><bold>Conclusion:</bold> The nano drug delivery system (TC‒mPEG‒PLGA) could target bone <italic>in vitro</italic> and <italic>in vivo</italic>, wherein it may be used as a novel delivery method for the enhancement of therapeutic effects of drugs with osteoporotic activity.</p>