Construction Of Oral Delivery Systems For Uric Acid Oxidase

Uric acid is the end product of purine metabolism in the body,and a diet heavy in purines tends to lead to the accumulation of uric acid,which causes gout.According to studies,gout is now the second most prevalent disease,after diabetes.Among the currently available medications for the clinical treatment of gout,uricase(UOX)is the most effective.However,the only uricase drugs currently available are injectable formulations,and the injection procedure causes patients pain while amplifying its side effects as an exogenous protein.Therefore,we must devise a novel method of employing uricase.Oral administration has significant advantages over injectable administration in terms of non-invasiveness,low threshold for use,and patient compliance.Due to its relatively unstable structure and large molecular weight,uricase encounters significant difficulties in the GI environment.Initially,we designed a formulation for slow-release tablets and evaluated their delivery and slow-release effects.Using the conventional tablet formulation design,a gel backbone sustained release tablet with hydroxypropylmethyl cellulose(HPMC)as the backbone was prepared to achieve the gradual release of uricase within 8h,with the final release exceeding 80%,laying the groundwork for the commercialization of oral uricase.Using contemporary materials and drug delivery technologies,we then developed two systems for the oral administration of uricase.First,we devised an anti-enzyme hydrogel delivery system with intestinal adhesion.Polyphenol oxidase catalyzed the green cross-linking of protease inhibitors on chitosan,and this modified chitosan was encapsulated on the surface of sodium alginate gel microspheres by electrostatic action.These hydrogels exhibited substantially enhanced resistance to protease degradation,the ability to maintain more than 80% urease activity in artificial intestinal fluid for6 hours,and adhesion to intestinal mucin solutions.Based on this,we developed a composite delivery system based on metal-organic framework material(MOF)and hydrogel,and achieved efficient encapsulation of uricase at ambient temperature and aqueous phase with a maximum loading rate of >30% through the bionic mineralization synthesis of ZIF-90,while enabling it to resist protease degradation nearly 100 percent within 6 h.Post-synthetic modification by sodium decanoate(C10)significantly improved the stability of the carrier in gastric acid and increased the uptake of the carrier by Caco-2 cells by 2-to 4-fold,while maintaining ATP-responsive release ability and rapid degradation and drug release at 5m M ATP concentration.To ensure efficient distribution of the system across the mucus layer,the carrier was finally encased in an anionic hydrogel.We have extended this research and discovered that this met hod can effectively deliver protein medications with varying molecular weights,making it a universal delivery system.