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Rezk, Abdelrahman I.,Obiweluozor, Francis O.,Choukrani, Ghizlane,Park, Chan Hee,Kim, Cheol Sang ELSEVIER 2019 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.141 No.-
<P><B>Abstract</B></P> <P>A pH-sensitive polymeric carrier was developed in this study for local delivery of anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on the conjugation of BTZ to polymeric carriers containing catechol groups, which are considered to release BTZ selectively in cancer cells. In this study we used alginate-conjugated polydopamine as a building block polymer. The catechol moiety of polydopamine binds to the boronic acid group of BTZ drug and release the drug molecules in a pH-dependent method. Cancer tissue has acidic environment where BTZ dissociate from the catechol group of polydopamine to control the release of the free drug. Mathematical equation models were used to clarify the mechanism of drug release. The release profile fitted first order with correlation coefficient (R<SUP>2</SUP> = 0.98), the release mechanism was studied using Korsmeyer–Peppas, Higuchi, Hixson-Crowell, and Kopcha models. We revealed the release mechanism follows non-fickian and diffusion was the dominant mechanism while small portion contributed to erosion. The pH-sensitive mechanism controls the release of BTZ in targeted cancer cells, hence developing a novel idea that is applicable in future towards other boronic acid-containing drugs to treat various kinds of health challenges.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The AlgPD-BTZ hydrogel presented a chemo selective approach for cancer chemotherapy. </LI> <LI> Sustained release profile of BTZ in pH dependent manner </LI> <LI> In-depth study of kinetics and mechanism of drug release </LI> <LI> The AlgPD-BTZ hydrogel shows remarkable cytotoxicity to cancer cells. </LI> </UL> </P>