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

Abstract

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. NP-gel­(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.

Hydrogels for dermal and transdermal drug delivery

“…An excellent antibacterial activity has also been obtained using platensimycin-loaded PAMAM dendrimers incorporated in a polyacrylamide gel. 196 Inorganic nanoparticles can also be charged with drugs, covalently attached on the surface of the particles or incorporated in pores inside the structure of the nanoparticles. Several systems made of inorganic nanoparticles have been developed for dermal or transdermal drug delivery, as metallic gold NPs, titanium dioxide, calcium phosphate or silica nanoparticles.…”

Polymeric Nanoparticles-Loaded Hydrogels for Biomedical Applications: A Systematic Review on In Vivo Findings

“…Skin is the largest organ and the first barrier of the human body against external influences [ 65 , 66 ]. Due to this constant exposure to the external environment, skin is constantly subject to wounds, which in turn are quite predisposed to inflammation or infection that make their healing difficult [ 67 ]. Beyond that, for patients with other comorbidities, such as diabetes, inflammation could be uncontrollable, and wound healing could turn into a chronic medical problem [ 68 ].…”

“…A promising approach to treat bacterial infections present either subcutaneously or in open wounds was proposed by Wang et al (2021) [ 67 ]. To this end, a PAM hydrogel containing PAMAM NPs was prepared for the controlled release of platensimycin, a natural antibiotic with great potential to treat infections caused by Staphylococcus aureus .…”

Advances in the Application of Nanomaterials as Treatments for Bacterial Infectious Diseases

“…A nanotechnology-based delivery method might provide a practicable way for therapy with these new antimicrobial agents. Platensimycin (PTM), a natural agent, could target bacterial fatty acid synthases and treat infections by MRSA [116]. To enable the usage of PTM in local MRSA infections, polyacrylamide hydrogels containing polyamidoamine was constructed for the organized release of PTM [116].…”

“…Platensimycin (PTM), a natural agent, could target bacterial fatty acid synthases and treat infections by MRSA [116]. To enable the usage of PTM in local MRSA infections, polyacrylamide hydrogels containing polyamidoamine was constructed for the organized release of PTM [116]. Luteolin-loaded methoxy poly-poly micelles could overcome the hydrophobicity and low oral bioavailability characters of luteolin.…”