4.7 Article

Nanoparticle-Hydrogel Systems Containing Platensimycin for Local Treatment of Methicillin-Resistant Staphylococcus aureus Infection

期刊

MOLECULAR PHARMACEUTICS
卷 18, 期 11, 页码 4099-4110

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.1c00523

关键词

antibiotics; platensimycin; nanoparticle-hydrogel; methicillin-resistant Staphylococcus aureus; skin and soft tissue infections

资金

  1. NSFC [81473124]
  2. Chinese Ministry of Education 111 Project [BP0820034]
  3. Open Sharing Fund for the Large-scale Instruments and Equipment of Central South University

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Research shows that hydrogels containing PTM nanoparticles can effectively treat skin infections caused by MRSA, not only exerting antibacterial effects but also accelerating wound healing, effectively treating subcutaneous tissue infections without toxicity.
Skin and soft tissue infections require effective and sustained topical administration. Platensimycin (PTM) is a natural drug lead that targets bacterial fatty acid synthases and has a great potential to treat infections caused by methicillin- resistant Staphylococcus aureus (MRSA). To facilitate the use of PTM against local MRSA infections, we prepared polyacrylamide hydrogels containing polyamidoamine (PAMAM)/PTM nanoparticles (NP-gel(PTM)) for the controlled release of PTM. NPgel(PTM) can continuously inhibit the growth of MRSA and its biofilm formation in simulated drug flow models in vitro. In situ implantation of NP-gel(PTM) could treat MRSA-infected subcutaneous soft tissues without toxicity. For MRSA-infected skin wounds, NP-gel(PTM) not only showed strong anti-MRSA activity but also accelerated more wound healing than the widely used antibiotic mupirocin. Collectively, PTM is expected to be used in this safe and effective NP-gel delivery platform for the treatment of local infections, which might help to alleviate the current antibiotic resistance crisis.

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