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Preparation and characterization of flexible nanoliposomes loaded with daptomycin, a novel antibiotic, for topical skin therapy

Authors Li C, Zhang X, Huang X, Wang X, Liao G, Chen Z

Received 16 December 2012

Accepted for publication 16 February 2013

Published 24 March 2013 Volume 2013:8(1) Pages 1285—1292


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Chong Li, Xiaolin Zhang, Xinliang Huang, Xiaoying Wang, Guojian Liao, Zhangbao Chen

College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China

Abstract: The purpose of this study was to investigate flexible nanoliposomes for mediating topical delivery of daptomycin, and to document permeation rates and bacteriostatic activity towards skin infections. Response surface methodology was used to optimize the daptomycin-loaded flexible nanoliposomes (DAP-FL), and the amount of drug loaded into the particles was evaluated as the investigation index. The optimal lipid ratio was lecithin to sodium cholate 17:1 (w/w) and the lipid to drug ratio was 14:1 (w/w). The hydration temperature was set at 37°C and the duration of treatment with ultrasound was 20 minutes. The DAP-FL obtained had a small mean particle size (55.4 nm) with a narrow size distribution (polydispersity index 0.15). The mean entrapment efficiency was 87.85% ± 2.15% and the mean percent drug loading was 5.61% ± 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 within 12 hours were measured at 96.28% ± 0.70% and (132.23 ± 17.73) µg/cm2 *5 = 661.15 ± 88.65 µg/cm2, directly, 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. These results demonstrate that the DAP-FL can enhance the ability of daptomycin to permeate the skin efficiently, where it has a powerful antibacterial action and activity against biofilms. This novel formulation of daptomycin has potential as a new approach in the clinical application of daptomycin.

Keywords: daptomycin, liposomes, response surface methodology, biofilm

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