Aim: Chitosan (CHS)-based nanoparticulate systems have gained much interest due to their high drug loading capacity and the simplicity of their fabrication. The physical properties of two types of curcumin-loaded CHS nanoparticles (CHS-NPs) were determined and compared. A new in-vitro release method was developed based on mathematical modeling in which the drug is first released from the NP into the surrounding medium and subsequently diffuses through the membrane. Methods: Curcumin-loaded CHS-NPs were fabricated by ionotropic gelation using sodium tripolyphosphate (TPP) and sodium hexametaphosphate (SHMP) crosslinking, and characterized by NP tracking analysis, loading capacity, zeta potential, Fourier transform infrared spectroscopy (FTIR), and in-vitro release rates. Results: The data showed that compared to SHMP crosslinked CHS-NPs, TPP crosslinking demonstrated a decrease in entrapment efficiency at a relatively high concentration of the agent, probably by narrowing the space between the polymeric chains. As indicated by zeta potential measurements, TPP crosslinking at all levels was more uniformly distributed inside the NPs, whereas the higher molecular weight SHMP at a low concentration creates NPs mostly by binding onto the surface. It was found that the release rates of curcumin from CHS-NPs crosslinked by SHMP at higher concentrations were about twice as high as the release rates of curcumin from TPP-crosslinked CHS-NPs, accompanied by notable lag times. Conclusions: This significant increase in the release rates of curcumin from SHMP-crosslinked CHS-NPs is explained by the large spatial structure of this crosslinker compared to the small TPP molecules. This study advances the literature on drug diffusion by making it possible to accurately determine its release from nanoparticulate systems.
Eydelman et al. (Wed,) studied this question.