Controlled curcumin release via conjugation into PBAE nanogels enhances mitochondrial protection against oxidative stress

Publication date: 25 September 2016 Source:International Journal of Pharmaceutics, Volume 511, Issue 2 Author(s): Prachi Gupta, Carolyn T. Jordan, Mihail I. Mitov, D. Allan Butterfield, J. Zach Hilt, Thomas D. Dziubla Mitochondria are considered to be the “power plants” of the cell, but can also initiate and execute cell death, stimulated by oxidative stress (OS). OS induced mitochondrial dysfunction is characterized by a loss in oxygen consumption and reduced ATP production. Curcumin, as a potential therapeutic, has been explored as a candidate for mitochondrial OS suppression, but rapid metabolism and aqueous insolubility has prevented it from being effective. Further, efficient delivery of curcumin via the incorporation into nanocarriers has again been limited due to low drug loading capacities and/or significant burst release, resulting in acute cytotoxicity. Hence, to increase the therapeutic potential and reduce the toxic effects of curcumin, curcumin conjugated poly(β-amino ester) nanogels (CNGs) were synthesized using Michael addition chemistry. This approach provided easy control over the nanogel size, with CNGs showing a uniform release of active curcumin over 48h with no burst release. This controlled release system significantly increased the safety limit for curcumin, with a ten fold increase in the cytotoxic threshold, as compared to free curcumin. Further, real-time mitochondrial response analysis with the Seahorse XF96 showed effective and prolong...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research