Fabrication of Polysaccharide-Based Nanoparticles as Drug Delivery Nanocarriers

Polysaccharide-based nanoparticles have been used to encapsulate drug within their matrices and then manipulated to release optimum doses of drug at targeted sites over a predictable period of time. Polysaccharide-based nanoparticles as drug delivery nanocarriers have afforded numerous advantages including enhanced therapeutic efficacy, minimized side effects, degradation prevention, and enhanced water solubility of drug molecules. Biopolymers or polysaccharides such as native or modified starches and regenerated celluloses have generated intense interests as precursors for the fabrication of nanoparticulate drug delivery systems due to their high biocompatibility, biodegradability, renewability, low toxicity, natural abundance and low cost.

Curcumin, a non-toxic bioactive polyphenol found in the rhizomes of turmeric (Curcuma longa), has attracted considerable attention due to its numerous pharmacological activities including anti-carcinogenic, anti-inflammatory, anti-proliferative and anti-oxidant activities. We have reported herein the successful loading of curcumin onto both native starch (NS) and starch-maleate (SM) nanoparticles under mild conditions using the water-in-oil emulsion and in-situ nanoprecipitation methods, respectively. Curcumin was observed to release from these nanoparticles in sustained and predictable manners. The physical and chemical properties of curcumin loaded polysaccharide-based nanoparticles such as sizes, porosity, and hydrophilicity or hydrophobicity were subsequently optimized by tailoring synthesis parameters such as ratios and types of solvents, surfactants and cross-linkers, as well as the nature of polysaccharide precursors. The main focuses of our research included mechanisms elucidation, modulation and optimization of the drug loading capacity and release kinetic profiles of polysaccharide-based drug delivery nanocarriers.

Under optimum conditions, curcumin loaded native starch (CurNS) nanoparticles  showed a mean diameter of 87 nm and exhibited a maximum loading efficiency of 78 %. Curcumin was observed to release from native starch nanoparticles in a sustained manner under physiological pH over a period of 10 days. On the other hand, curcumin loaded starch-maleate (CurSM) nanoparticles showed a wide range of diameter between 30 nm and 110 nm with a mean diameter of about 50 nm. The loading of curcumin onto starch-maleate nanoparticles occurred rapidly initially but declined gradually until the curcumin loading capacity of 15 mg/g was reached within 12 hours. Both curcumin-loaded native starch (CurNS) and starch-maleate (CurSM) nanoparticles were observed to exhibit substantially enhanced water solubility as compared to that of free curcumin. CurSM nanoparticles exhibited a water solubility of 6.0 x 10^-2 mg/mL which was about 300 times higher than that of free curcumin. Increased water solubility coupled with desirable loading capacity and release kinetic profile should, in turn, lead to enhanced bioavailability of curcumin. The potential utility of native starch and starch-maleate nanoparticles as efficient and cost-effective drug delivery nanocarriers is envisaged.