Study On The Transdermal Drug Delivery System Of Daptomycin

Daptomycin is a lipopeptide antibiotic first approved by the FDA, which has excellent effects on killing anti-Gram-positive bacteria. Daptomycin is activity limited to gram-posotive organisms, especially the antibiotic-resistant bacteria. Cubicin R (daptomycin for injection, Cubist Pharmaceuticals Inc, Lexington, MA) is the only approved once-daily treatment available for complex skin and skin structure infections caused by susceptible strains of Gram-positive micro-organisms and S. aureus bloodstream infections in the United States. And there isn’t any other dosages about daptomycin be reported. Considering the patient compliance and drug distribution in the target tissues, there is a pressing need to develop new dosage formulations of daptomycin to satisfy a range of therapeutic requirements. This study developed daptomycin transdermal delivery system for topical skin therapy. The formulation was optimized via response surface methodology. The physicochemical properties of the optimized Daptomycin preparation were characterized, and their bioactivity against S. aureus and biofilms was evaluated both in vitro and in vivo. And also explored the HPLC test case of Daptomycin. The major research contents and results are as follows:1the test case of daptomycinDiamonsil C18chromatographic column (150mm×R4.6mm,5μm); the mobile phase: acetonitrile-0.5%ammonium phosphate buffer (36:64); The detection wavelength:221nm; the flow velocity:1mL-min"1; the retention time:6.7+0.2min; the lowest detection limit: 0.8ng.2Valuation about the two type of datomycin ointmentThe best prescriptions of datomycin ointment, follow as, the prescriptions of O/W:white petrolatum17.00g, octadecanol20.00g, propanediol10.00g, sodium lauryl sulfate1.50g, water50.00g, calcium chloride0.50g, daptomycin1.00g. the prescriptions of W/O: octadecanoic acid5.00g, glycerin monostearate15.00g, liquid paraffin14.00g, white petrolatum15.00g, water saturated with calcium hydroxide50.00g, daptonycin1.00g.Skin permeation study in vitro showed that, the cumulative percentage of O/W ointment daptomycin permeated through the skin was53.35%within the first8hours, the cumulative percentage of W/O ointment daptomycin was44.15%, After6hours, almost all of the daptomycin had penetrated through the skinPharmacodynamic study showed that, the cumulative amount of daptomycin permeated through the skin haved obvious bacteriostasis effect, and can prevent the from of biofilm.3Valuation about the datomycin transfersomesThe optimal lipid ratio was lecithin to sodium cholate17:1(w/w) and the lipid to drug ratio was14:1(w/w). The hydration temperature was set at378℃and the duration of treatment with ultrasound was20minutes.The datomycin transfersomes obtained had a small mean particle size (55.4nm) with a narrow size distribution (polydispersity index0.15). The mean entrapment efficiency was87.85±2.15%and the mean percent drug loading was5.61±0.14%.Using skin mounted between the donor and receptor compartments of a modified Franz diffusion cell, the percentage and quantity of cumulative daptomycin permeation from DAP-FL within12hours were measured at96.28±0.70%and136.59±17.68±g/cm2, respectively, showing rapid and efficient antibacterial activity against Staphylococcus aureus. Following local administration of DAP-FL, daptomycin was detected in multilayer tissues within the skin and underlying structures in the dorsal skin of the mouse. Effective therapeutic concentrations were maintained for several hours, and significantly inhibited bacterial growth and injury-induced biofilms.