Conjugate Of Dapsone And Sodium Alginate: Design,Preparation And Release Investigation

Dapsone(DS)is the preferred choice for the treatment of leprosy and its various indications have also been studied including autoimmune skin diseases,malaria,rheumatism arthritis,and pneumoniae pneumonia.However,the clinical practice of dapsone is severely limited because of its non-specific distribution in the body after oral administration and serious side effects of hemolysis and methemoglobinemia.In order to reduce these sides effect and drug dosage,the sodium alginate was used as a durg carrier to prepare the topical agents through physical interaction and chemical bonds with dapsone,and drug release both in vitro and in vivo was also evaluated.In this study,dapsone microspheres and conjugates were prepared by calcium ions crossing linker and valine linking arm separately,and characterized bya series of methods.Though with a sustained release effect within 32 h in vitro,dapsone calcium alginate couldn?t prevent the release of drug.In vitro experiments showed that drug released completely within 8 h from the physical mixture of dapsone and sodium alginate However,there was no drug release from covalent conjugates to dissolution medium.Indicating that the covalent conjugates could avoid drug separate from alginate carrier to diffuse.Furthermore,the diffusion ability of dapsone-sodium alginate physical mixture and conjugates into animal?s circulation was evaluated by administration in the local skin trauma(scald).A certain amount of drug was detected in the plasma of rats with dapsone-sodium alginate solid dispersion and AUC was 31.78(?g·h/ml).However,there was no drug detected in the rats with dapsone-sodium alginate conjugates.It is suggested that the combination of dapsone to sodium alginate by covalent bond could effectively control the release of drugsand prevent drug from entering systemic circulation.The controlled drug release and topical administration could not only avoid non-specific distribution as wellas serious side effects but also increase the local drug concentration and promote wound treatment efficacy.