The Acne Treatment By The Combined Use Of Marine Antimicrobial Peptides And Sponge Haliclona Sp.spicules

Acne is a chronic inflammatory disease of the pilosebaceous unit that can affect people of all age groups and is most prevalent in adolescence.Acne affects approximately 85%of teenagers.In the multifactorial pathogenesis of acne,Propionibacterium acnes(P.acnes)colonization is one of the main factors.In the past 40 years,antibiotics have been the mainstays drug for the treatment of acne against P.acnes.However,the long-term use of antibiotics has led to the cross-resistance of P.acnes,it is necessary to find effective drugs to alternative antibiotics.Because of their broad-spectrum antimicrobial activity and their low rates of resistance,antimicrobial peptides(AMPs)are now being extensively studied.Antibacterial peptides are regarded as one of the effective drugs instead of antibiotics and have broad clinical application prospects.The study of the antimicrobial activity of antimicrobial peptide against P.acnes proved that Sph12-38,Sphistin and AMP-X1 had antimicrobial activity against P.acnes with minimum bactericidal concentration(MBC)values under 24 μM.Sph12-38 has a significant bactericidal effect on P.acnes with a MBC value of 7 μM.The antibacterial mechanism of the Sph12-38 against P.acnes was explained preliminarily.After incubation with Sph12-38,P.acnes has obvious morphological perturbations,rougher surface and blebs.Meanwhile,it was proved by MTT assay that the Sph12-38 had no significant cytotoxicity to human keratinocytes(HKs)and had no significant effect on the morphology of HKs.The safety of was indicated.In vitro skin penetration study of Sph12-38 demonstrated that the topically application of sponge Haliclona sp.spicules(SHS)can result in the microchannel on the surface of the skin are continuous and improve the penetration of Sphl2-38.Specifically,penetration of FITC-Sph12-38 into porcine skin in vitro up to 40.91±5.85%,which is 6.13±0.87-fold higher than Phosphate Buffered Saline(PBS)group.The combined use of Sphl2-38 and SHS can increase the accumulation of Sph12-38 in epidermis and dermis for and kill P.acnes in the pilosebaceous unit.In the treatment of acne model study,the values of acne height,number and diameter were reduced in the combined use of Sph12-38 and SHS group.After treatment with Sph12-38 and SHS in rabbit ear,the degree of inflammatory infiltration and expansion of pilosebaceous were reduced.The combined use of Sph 12-38 and SHS is one of the methods to treat rabbit ear acne,which has short treatment time and obvious effects.We showed for the first time that Sph12-38 have antimicrobial activity against P.acnes and is a safe and effective drug for the clinical treatment of acne.The penetration of the Sph 12-38 was promoted by combinated use of Sph12-38 SHS.The use of SHS promotes the skin penetration of biomacromolecules,overcomes the drawbacks of microneedle,and has the characteristics of efficent penetration and convenience,providing a safe and effective method for the drug delivery.