Synthesis and Release of Dapsone-Alginate (DS-Alg) Conjugate / 中国药学杂志

ABSTRACT

OBJECTIVE: To synthesize and characterize dapsone-alginate acid (DS-ALG) conjugate. METHODS: Alginate (Alg) was selected as the drug carrier and valine (Val) as the linking arm to synthesize DS-Alg, which could be applied to topical administration. And the synthetic condition of DS-Alg was optimized by changing the amount of 1-(3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), while the pH of solvent was changed in the range of 4.0 to 6.0. The structures of the products were characterized by 1H-NMR, MS and FT-IR. Meanwhile, the drug release in vitro of DS-Alg was investigated in the mixture of pH 7.4, 0.05 mol•L -1 PBS and ethanol by diffusion cells. The concentration of DS or valine-dapsone in the release medium was detected by HPLC. Taking rats with local scald as model, the drug release in vivo was measured by coating the trauma with DS-Alg conjugate cream and monitoring the drug concentration in blood. RESULTS: The optimum synthetic conditions of DS-Alg were as follows 0.277 g valine-dapsone, 0.400 g sodium alginate, 7 eq EDC, 3 eq NHS, pH of the solvent of 5.5. And during 72 h, there was no DS detected in the release medium or rat plasma. The AUC0→72 h of DS-Alg was 0. It suggested that DS immobilized by Alg with covalent bond was too stable to be released from Alg in vitro and in vivo. The DS-Alg conjugate could effectively prevent DS from entering the systemic circulation. CONCLUSION: DS-Alg conjugate is successfully synthesized. The conjugate is stable that DS cannot be released from the conjugate to the bloodstream, which can efficiently decrease the side effects of DS and has the potential for topical administration.