Development Of A Chitosan-based Nanoparticle Formulation For Ophthalmic Delivery Of Honokiol

Chitosan(CS),an extensively studied water-soluble polymer produced through chitin deacetylation,is a non-toxic,biodegradable,biocompatible,and positively charged compound.Chitosan nanoparticles were prepared according to the ionotropic gelation method and widely used in ocular drug delivery system.Sulfobutylether-β-cyclodextrin(SCD)is an anion,highly water soluble β-cyclodextrin derivative,and can increase the solubility of poorly soluble drugs.Therefore,in this study,we prepared chitosan/sulfobutylether-β-cyclodextrin nanoparticles to improve the solubility of drug and prolong the drug residence time,thereby enhancing the bioavailability of the drug.The main contents of this study were listed below:1.The establishment of in vitro analysis of honokiol.2.Preparation of honokiol-loaded chitosan/sulfobutylether-β-cyclodextrin nanoparticles and its properties.3.Pharmacokinetic study of honokiol-loaded chitosan/sulfobutylether β-cyclodextrin nanoparticles in vivo.An UV spectrophotometric method for the determination of honokiol(HK)was established.The detection wavelength of HK was 292 nm.The absorbance showed a good linear relationship in concentration range of 6.0~30.0μg·mL-1.Intra-day and inter-day precision were in line with the requirements of methodology.Honokiol-loaded chitosan/sulfobutylether-β-cyclodextrin nanoparticles(HK-CS-NPs)were prepared according to the ionotropic gelation method.Then observed their characterization(such as encapsulation efficiency,particle size and Zeta potential)and determined release behavior of HK.Meanwhile,HK-CS-NPs were characterized by Fourier transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).These nanoparticles were regular and spherical in shape,within the nano-sized range(373.40–523.30 nm)and displayed a positive zeta potential(+24.2 to +19.9 mV).The encapsulation efficiency of HK in nanoparticles ranged from 25.49% to 84.92%.Results of the in vitro release indicated that HK-CS-NPs achieved superior sustained-release effects.Eye irritation was evaluated according to Draize test to evaluate the applicability of HK-CS-NPs.The results showed that HK-CS-NPs might be safe applied for ophthalmic drug delivery.Meanwhile,in vivo study also revealed that HK-CS-NPs could significantly increase HK bioavailability in the aqueous humor compared with that HK-sus.In conclusion,this study proposes HK-CS-NPs as a potential ophthalmic delivery system for retinal neovascularization.