Glucan - Dopamine And Chitosan - Him Before Methadone Macromolecules Synthesis Of Drugs And Drug Controlled Release

Macromolecular prodrugs of metaxalone and dopamine were prepared and characterized through various technologies.The controlled release studies were performed in various media.Dopamine(DA) was covalently linked to dextran via succinic anhydride spacer. The average molecular weight used for dextran are 20000 and 40000,respectively, and the procedure of chemical modification for dextrans was conducted by a twostep: (1) preparation of dextran having carboxylic end groups;(2) synthesis of D20000-DA and D40000-DA.The two prodrugs were characterized by DSC and IR analysis.The release studies were performed in pH 1.1,7.4 and 9.0 buffer solutions, The results demonstrated that,under the same condition,the release rate of dopamine for D40000-DA is slower than that of D20000-DA.Methoxy poly(ethylene glycol) was covalently linked to chitosan via succinic anhydride spacer.The procedure of chemical modification for chitosan was conducted by a four-step protocol:(1) synthesis of N-succinyl-chitosan;(2) synthesis of N-succinyl-chitosan-mPEG;(3) synthesis of N-chloroacetyl-metaxalone; (4) synthesis of CS-mPEG-Met.The controlled drug release studies were performed in buffer solutions with pH values equal to 1.1,7.4 and 10.0.In the present of parenzyme andα-chymotrypsin,the release studies were performed in pH=8.0 buffer solutions.More amounts of metaxalone and dopamine can be detected releasing from polymer-drug conjugate at the presence ofα-chymotrypsin and parenzyme compared with its absence.The three novel macromolecular prodrugs can improve the pharmacokinetics of dopamine and metaxalone, particularly by increasing its half-life period.