Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Surgery-Plastic Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Macromol Biosci. 2024 May;24(5):e2300519. doi: 10.1002/mabi.202300519. Epub 2024 Jan 20.
Wound biofilms pose a great clinical challenge. Herein, this work reports a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti-PBP2a and engineers antimicrobial peptides W379. In vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng mL W379 and 250 ng mL anti-BPB2a decreases the bacterial count from ≈3.31 × 10 CFU mL to 1.28 × 10 CFU mL within 2 h without eliciting evident cytotoxicity. Ex vivo testing indicates W379 and anti-PBP2a co-loaded microneedle patch displayed a remarkable reduction of bacterial load by ≈7.18 log CFU after administered only once within 48 h. The bacterial count is significantly diminished compared to the treatment by either W379 or anti-PBP2a-loaded alone microneedle patches. When administered twice within 48 h, no bacteria are identified. Further in vivo study also reveals that after two treatments of W379 and anti-PBP2a co-loaded PVP microneedle patches within 48 h, the bacterial colonies are undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti-PBP2a co-loaded PVP microneedle patches hold great promise in treating wound biofilms.
伤口生物膜带来了巨大的临床挑战。在此，本工作报道了一种可溶解的微针贴片，用于双重递送达托霉素和工程抗菌肽 W379。含有 250 ng/mL W379 和 250 ng/mL 抗 PBP2a 的微针贴片的体外抗菌功效测试表明，在 2 小时内，细菌数量从约 3.31×10CFU/mL 减少至 1.28×10CFU/mL，而没有引起明显的细胞毒性。离体试验表明，在 48 小时内仅给药一次，载有 W379 和抗 PBP2a 的微针贴片可使细菌载量显著降低约 7.18 log CFU。与单独使用 W379 或抗 PBP2a 负载的微针贴片相比，细菌数量明显减少。在 48 小时内给药两次时，未检测到细菌。进一步的体内研究还表明，在 II 型糖尿病小鼠伤口生物膜模型中，在 48 小时内两次给予载有 W379 和抗 PBP2a 的 PVP 微针贴片后，细菌菌落无法检测到。综上所述，载有 W379 和抗 PBP2a 的 PVP 微针贴片在治疗伤口生物膜方面具有广阔的应用前景。
