Preparation of water-soluble chitosan oligosaccharides by oxidative hydrolysis of chitosan powder with hydrogen peroxide.

Chitosan (CS) is only soluble in weak acid medium, thereby limiting its wide utilisation in the field of biomedicine, food, and agriculture. In this report, we present a method for preparing water-soluble CS oligosaccharides (COSs) at high concentration (∼10%, w/v) via the oxidative hydrolysis of CS powder with molecular weight (Mw) ∼90,000 g/mol) in 2% H2O2 solution at ambient temperature by a two-step process, namely, the heterogeneous hydrolysis step and homogeneous hydrolysis step. The resultant COSs were characterised by gel permeation chromatography (GPC), fourier transforms infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), proton nuclear magnetic resonance spectroscopy (1H NMR) and X-ray diffraction (XRD) spectroscopy. The resulting products were composed of COSs (Mw of 2000-6600 g/mol) that were completely soluble in water. The results also indicated that the structure of COSs was almost unchanged compared with the original CS unless Mw was low. Accordingly, COSs with low Mw (∼2000 g/mol) and high concentration (10%, w/v) could be effectively prepared by the oxidative hydrolysis of CS powder using hydrogen peroxide under ambient conditions.

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 <24 h for the CUR-CHI nanoplex). At the optimal condition, the CUR-OCHI nanoplex (without ultrasonication) exhibited size, zeta potential, and CUR payload of ≈140 nm, 20 mV, and 78% (w/w), respectively. The nanoplex preparation was simple yet robust at nearly 100% CUR utilization rate. The CUR-OCHI nanoplex exhibited superior wound healing efficacy to the native CUR with wound closure of >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.