The Investigation Of Preparation And In Vitro/vivo Evaluation Of NYT Flexible Liposomal Gel

NYT and Amphotericin B (AmB) are two structurally similar polyene macrolideantibiotics characterized by a potent broad-spectrum antifungal action. Nowadays,AmB is still the most common antifungal agent that used to treat systemic fungalinfections. Since NYT has different biological properties from those of AmB andsometimes acts on AmB-resistant fungi, the intravenous administration of NYT wouldbe desirable. NYT, on the other hand, is only used topically, as it is ineffective orallyand severely toxic when administered intravenously. One of the possibilities forincreasing dissolubility of durgs is liposomes. Classic liposomes are of little value ascarriers for drug delivery via the skin. Inorder to development of applications of NYTin local drug treatment for fungal skin infections Liposomes are tiny spheres rangingin diameter from50nm to150nm. The incorporation of some additives such asanionic surfactants and ethanol can fluidize the phospholipid bilayers, thus increasingthe depths to which liposomes can penetrate into the intercellular pathways of theskin.First，we established HPLC method to assay of the content of the nystatin inflexible liposomes, and the encapsulation efficiency in liposme was evaluation.central composite method was used to optimize three factors of prescription:CHL:PC=1:8.49, NYT:PC=1:3.91,V(hydration):NYT=115.64:1, Maximum encapsulationefficiency was95.62%which is5%higher than before。On basis of central composite experiment, we constructed a desirability functionto evaluat NYT percutaneous penetration synthetically. respectively, the proportion ofsodium cholate and ethanol affact the value of desirability function and when the ratioof sodium cholate was one fourth of PC, the ethanol concentration was30%, thevalue of desirability function is maximal. on this condition, NYT flexible liposome isstabile.To increase the residence time of the the NYT flexible liposomes on the skin, wecame to carbopol gel. The value to the desirability function as response, we design aorthogonal experimental method to optimize the prescription of NYT flexibleliposomal gel.As a result, the optimal conditions was A2B2C2D3, namely carbomerconcentration of1.5%, the drug content of15mg/mL of glycerol content of3%, thepH value of7:00. On the condition of optimal prescribing, average of the steady stateflux of NYT weighted21.34μg cm-2h-1, intradermal stranded52.67μg cm-2. We also estimated stability, skin irritation and in vitro antibacterial activity ofNYT flexible liposomal gel. The results show that NYT flexible liposomal gel isstabile, without skin irritation in vitro,and antifungal in vivo.