Fabrication of Nanoparticles to Treat Methicillin-resistant Staphylococcus Aureus
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Date
2015-11-11
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Abstract
Staphylococcus aureus (SA) lung infections are a major problem for patients with cystic fibrous (CF). As these infections are difficult to treat, they can be life-threatening.1 Moreover, methicillin-resistant Staphylococcus aureus (MRSA) strains have become more prevalent and often exhibit resistance to first line antibiotics, including vancomycin, clindamycin, and trimethoprim/sulfamethoxazole.2 A natural product, MC21-A (C58), from a marine bacteria, Pseudoalteromonas phenolica, has potent activity against MRSA. However, the compound is hydrophobic; thus, delivery in an aqueous solution is problematic.3 In order to optimize the efficacy of this drug candidate to treat MRSA lung infections, it must pass through the thick mucus in the CF airway to reach the bacteria. Encapsulating C58 in a polymeric nanoparticle can improve penetration into and retention in mucus and bacterial biofilms. In particular, nanoparticles coated with polyethylene glycol (PEG) have been shown to rapidly penetrate human mucus.4 We have developed a simple, scalable method for production of poly (lactic-co- glycolic acid) (PLGA) nanoparticles coated with PEG that allows large-scale production of this “workhorse” nanoparticle system. These nanoparticles will allow further testing of this drug and other potential candidates to proceed to clinical testing for treatment of MRSA lung infections in CF patients.
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methicillin-resistant Staphylococcus aureus, cystic fibrosis, poly(lactic-co-glycolic acid)