Eckhard Lea H, Houri-Haddad Yael, Sol Asaf, Zeharia Rotem, Shai Yechiel, Beyth Shaul, Domb Abraham J, Bachrach Gilad, Beyth Nurit
Department of Prosthodontics, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
Institute of Dental Science, the Hebrew University-Faculty of Dental Medicine, Jerusalem, Israel.
PLoS One. 2016 Sep 8;11(9):e0162537. doi: 10.1371/journal.pone.0162537. eCollection 2016.
The development of antibacterial drugs to overcome various pathogenic species, which inhabit the oral cavity, faces several challenges, such as salivary flow and enzymatic activity that restrict dosage retention. Owing to their amphipathic nature, antimicrobial peptides (AMPs) serve as the first line of defense of the innate immune system. The ability to synthesize different types of AMPs enables exploitation of their advantages as alternatives to antibiotics. Sustained release of AMPs incorporated in biodegradable polymers can be advantageous in maintaining high levels of the peptides. In this study, four potent ultra-short lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO) and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained release. The lipopeptide and polymer formulations were tested for antibacterial activity during one week, by turbidometric measurements of bacterial outgrowth, anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and XTT colorimetric assays, mode of action by fluorescence-activated cell sorting (FACS) and release profile by a fluorometric assay. The results show that an antibacterial and anti-biofilm effect, as well as membrane disruption, can be achieved by the use of a formulation of lipopeptide incorporated in biodegradable polymer.
开发用于对抗口腔中各种致病菌种的抗菌药物面临着诸多挑战，例如唾液流动和酶活性会限制药物剂量的留存。抗菌肽（AMPs）因其两亲性，成为天然免疫系统的第一道防线。能够合成不同类型的抗菌肽，使得利用其优势作为抗生素的替代品成为可能。将抗菌肽掺入可生物降解聚合物中实现持续释放，可能有助于维持高浓度的肽。在本研究中，四种与脂肪酸链（16C）共轭的强效超短脂肽被掺入两种不同的可生物降解聚合物中：聚（乳酸 - 共蓖麻油）（PLACO）和基于蓖麻油酸的聚（酯 - 酸酐）（P(SA - RA)），以实现持续释放。通过比浊法测量细菌生长来测试脂肽和聚合物制剂在一周内的抗菌活性，通过活/死染色测试抗生物膜活性，通过溶血和XTT比色法测试生物相容性，通过荧光激活细胞分选（FACS）测试作用模式，并通过荧光测定法测试释放曲线。结果表明，使用掺入可生物降解聚合物中的脂肽制剂可实现抗菌和抗生物膜效果以及膜破坏。
