What are parameters affecting Leu-enkephalin loading and release from poly(isobutylcyanoacrylate) nanoparticles coated with thiolated chitosan?

This work aimed to investigate the loading and the release of Leu-enkephalin from chitosan and thiolated chitosan-coated poly(isobutylcyanoacrylate) nanoparticles by modifying different parameters : chitosan molecular weight (Mw 30, 85 and 145 kg/mol), its degree of thiolation and incorporation of poly(methylmethacrylate) in the nanoparticle core. According to the results, the main parameter controlling the loading and the release of Leu-enkephalin was the composition of the nanoparticle shell. Indeed, it was found that loading was higher and the release was most delayed when chitosan Mw was low. Furthermore, there was a clear trend to a better control of Leu-enkephalin release with low thiolated-chitosan proportion. As demonstrated by using isothermal titration microcalorimetry (ITC) experiments, low thiolated-chitosan proportion corresponds to a higher amount of functional amino-groups able to interact with the negative charge found on Leu-enkephalin. In contrast, the incorporation of poly(methylmethacrylate) in the nanoparticle core did not slow-down the release of Leu-enkephalin but enhanced the burst release effect.