Preparation and characterization of nanoparticles based on poly(ethyleneglycol) methacrylate grafted chitosan for intraocular adminsigtration of antibiotics

摘要

Introduction: The present work is dealing with the preparation and characterisation of nanopartides based on chemically modified chitosan especially designed for intraocular administration of antibiotics. Materials and Methods: The grafting reaction of chitosan (CS) with poly(ethylene glycol) methacrylate (PEGMA) has been performed by Michael addition and we intended this way to improve the water solubility of chitosan, being well known that the latter is only soluble in acid conditions. The chitosan grafting and grafting degree have been analysed by NMR and FTIR. The preparation of the nanopartides based on the modified chitosan has been made by the method of the double crosslinking using sodium tripolyphosphate (ionic crosslinking) and glutaraldehyde (covalent crosslinking) in reverse emulsion, the process being optimized through the modification of certain reaction parameters (polymer ratio, stirring rate, crosslinker amount, etc.). The particles with optimal characteristics (Figure 1) (in terms of morphology, water swelling degree, zeta potential) have been analyzed from the point of view of the capacity of inclusion/release of drugs and tested in vitro and ex vivo for their release ability through corneal membrane using a Franz Cell device. For loading and release studies, levofloxacin has been used for analysing the nanopartides potential applications in the treatment of ophthalmic infections. Figure 1: Scanning Electron microscopy image of CS-PEGMA particle Results and Discussion: The properties of nanopartides in terms of morphology, swelling, drug loading/release capacity will be discussed taking into account the new polymer properties and with the crosslinking reaction parameters. The advantages of these systems which are related to biocompatibility, mucus adhesiveness, penetration of ocular barriers, biodistribution on the ocular level, increased resistance period of the drugs, as well as biodegradability, recommend them successfully for ophthalmic applications. During this study encouraging results were obtained regarding their potential application for the treatment of ocular infections Conclusions: Nanopartides based on PEGMA grafted chitosan represent a reliable solution for the treatment of ocular infections. Further investigations including in vivo tests for testing their ability to release the antibiotics and intraocular biodistribution of nanopartides are envisaged.