A simple strategy to enhance the in vivo wound-healing activity of curcumin in the form of self-assembled nanoparticle complex of curcumin and oligochitosan

While the wound healing activity of curcumin (CUR) has been well-established, its clinical effectiveness remains limited due to the inherently low aqueous CUR solubility, resulting in suboptimal CUR exposure in the wound sites. Previously, we developed high-payload amorphous nanoparticle complex (or nanoplex) of CUR and chitosan (CHI) capable of CUR solubility enhancement by drug-polyelectrolyte complexation. The CUR-CHI nanoplex, however, exhibited poor colloidal stability due to its strong agglomeration tendency. Herein we hypothesized that the colloidal stability could be improved by replacing CHI with its oligomers (OCHI) owed to the better charge distribution in OCHI. The effects of key parameters in drug-polyelectrolyte complexation (i.e. pH, salt inclusion, CUR concentration, and OCHI/CUR charge ratio) on the physical characteristics and preparation efficiency of the CUR-OCHI nanoplex produced were investigated. The in vivo wound healing efficacy of the CUR-OCHI nanoplex and its cytotoxicity towards human keratinocytes cells were examined. The results showed that CUR-OCHI nanoplex exhibited prolonged colloidal stability (72 h versus 90% after 7 days versus 9 days for the native CUR resulting in smaller scars, attributed to its generation of high CUR concentration in the wound sites.Nanyang Technological UniversityAccepted versionThe authors would like to acknowledge the research funds from Vietnam Atomic Energy Institute and Nuclear Research Institute (Grant number: 07/17/VNCHN) and from Nanyang Technological University's Undergraduate Research Experience on Campus (URECA) for Suen Ern Lee