Bioactivity of WLBU2 peptide antibiotic in combination with bioerodible polymer
Bioactivity of WLBU2 peptide antibiotic in combination with bioerodible polymer
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DOI：
10.1016/j.ijantimicag.2011.07.011
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发表时间：
2011-12-01
影响因子：
10.8
通讯作者：
Puleo, D. A.
中科院分区：
文献类型：
--
作者：
McClanahan, J. R.;Peyyala, R.;Puleo, D. A.
WLBU 2是一种肽抗生素，具有广泛的抗菌活性，包括与牙周病相关的细菌。虽然牙周炎与各种全身性疾病有关，从心血管疾病到早产，但需要局部治疗来治疗感染源。生物可降解聚合物通常用于局部控制药物的递送量和速率。在本研究中，探索了包含邻苯二甲酸乙酸纤维素（CAP）和Pluronic（R）F-127（PF-127）的生物可蚀性缔合聚合物与WLBU 2的相互作用。CAP/PF-127的固有抗微生物活性以及聚合物和WLBU 2的组合作用使用参与牙齿表面早期定殖的戈登链球菌（Streptococcus gordonii）进行检查。单独的聚合物共混物具有剂量依赖性的抑菌性质，导致在测试的最高浓度下菌落的>= 2 log减少，这可能是由于CAP的疏水性破坏细菌表面。当WLBU 2与CAP/PF-127组合时，与游离WLBU 2相比，肽与聚合物的表观结合显著降低了活性，游离WLBU 2通过使细菌膜不稳定而像其他阳离子肽一样起作用。用蔗糖作为赋形剂的制剂，其减少了WLBU 2和聚合物之间的相互作用，恢复了肽抗生素的杀菌活性，如S. gordonii。WLBU 2可以使用CAP/PF-127作为释放载体进行局部递送，该肽的杀菌活性主导了聚合物的抑菌作用。(C)2011年爱思唯尔B。和国际化疗学会。All rights reserved.
WLBU2 is a peptide antibiotic designed for broad antimicrobial activity, including bacteria associated with periodontal disease. Although periodontitis is associated with various systemic conditions, ranging from cardiovascular disease to preterm birth, local therapy is needed to treat the source of infection. Biodegradable polymers are often used to control locally the amount and rate of delivery of drugs. In the present study, a bioerodible association polymer comprising cellulose acetate phthalate (CAP) and Pluronic (R) F-127 (PF-127) was explored for its interaction with WLBU2. The intrinsic antimicrobial activity of CAP/PF-127 and the combined effects of the polymer and WLBU2 were examined using Streptococcus gordonii, a species involved in early colonisation of tooth surfaces. The polymer blend alone had dose-dependent bacteriostatic properties, resulting in a >= 2 log decrease in colonies at the highest concentrations tested, possibly due to the hydrophobicity of CAP disrupting the surface of bacteria. When WLBU2 was combined with CAP/PF-127, an apparent binding of peptide to polymer significantly decreased the activity compared with free WLBU2, which functions like other cationic peptides by destabilising the bacterial membrane. Formulation with sucrose as an excipient, which reduced the interaction between WLBU2 and polymer, restored the bactericidal activity of the peptide antibiotic as reflected by a >3 log decrease in S. gordonii. WLBU2 can be locally delivered using CAP/PF-127 as a release vehicle, with the peptide's bactericidal activity dominating the polymer's bacteriostatic effect. (C) 2011 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.