Desai, H., M. Y. Mahmoud, J. Tan, F. Minooei, D. R. Demuth, and J. M. Steinbach-Rankins, "Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms ", Pharmaceutics, vol. 12 , issue 9, pp. 835, 2020.
Mahmoud, M. Y., S. Sapare, K. C. Curry, D. R. Demuth, and J. M. Steinbach-Rankins, "Rapid Release Polymeric Fibers for Inhibition of Adherence to .", Frontiers in chemistry, vol. 7, pp. 926, 2019. Abstract

Active agents targeting key bacterial interactions that initiate biofilm formation in the oral cavity, may alter periodontitis progression; however, to date, specifically-targeted prophylactic and treatment strategies have been limited. Previously we developed a peptide, BAR (SspB Adherence Region), that inhibits oral biofilm formation and , and BAR nanoparticles that increase BAR effectiveness via multivalency and prolonged delivery. However, limited BAR loading and nanoparticle retention in the oral cavity can result in inadequate release and efficaciousness. Given this, an effective delivery platform that can release concentrations of BAR suitable for twice-daily applications, may offer an alternative that enhances loading, ease of administration, and retention in the oral cavity. With this in mind, the study objectives were to develop and characterize a rapid-release platform, composed of polymeric electrospun fibers (EFs) that encapsulate BAR, and to evaluate fiber safety and functionality against / biofilms . Poly(lactic-co-glycolic acid) (PLGA), poly(L-lactic acid) (PLLA), and polycaprolactone (PCL) were electrospun alone or blended with polyethylene oxide (PEO), to provide high BAR loading and rapid-release. The most promising formulation, 10:90 PLGA:PEO EFs, provided 95% BAR release after 4 h, dose-dependent inhibition of biofilm formation (IC50 = 1.3 μM), disruption of established dual-species biofilms (IC50 = 2 μM), and maintained high cell viability. These results suggest that BAR-incorporated EFs may provide a safe and specifically-targeted rapid-release platform to inhibit and disrupt dual-species biofilms, that we envision may be applied twice-daily to exert prophylactic effect in the oral cavity.

Tyo, K. M., A. B. Lasnik, L. Zhang, M. Mahmoud, A. B. Jenson, J. L. Fuqua, K. E. Palmer, and J. M. Steinbach-Rankins, "Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections.", Journal of controlled release : official journal of the Controlled Release Society, vol. 321, pp. 84-99, 2020. Abstract

Human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide. The antiviral lectin, Griffithsin (GRFT), has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo. The goal of this work was to develop a multilayered nanoparticle (NP)-electrospun fiber (EF) composite to provide sustained-release of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection. Composites were fabricated from polycaprolactone (PCL) fibers surrounding polyethylene oxide (PEO) fibers that incorporated methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) GRFT NPs. GRFT loading and release were determined via ELISA, showing that NP-EF composites achieved high GRFT loading, and provided sustained-release of GRFT for up to 90 d. The in vitro efficacy of GRFT NP-EFs was assessed using HIV-1 pseudovirus assays, demonstrating complete in vitro protection against HIV-1 infection. Additionally, sustained-release NP-EFs, administered 24 h prior to infection, prevented against a lethal dose of HSV-2 infection in a murine model. In parallel, histology and cytokine expression from murine reproductive tracts and vaginal lavages collected 24 and 72 h post-administration were similar to untreated mice, suggesting that NP-EF composites may be a promising and safe sustained-delivery platform to prevent HSV-2 infection. Future work will evaluate the ability to provide prolonged protection against multiple virus challenges, and different administration times with respect to infection.

Sims, L. B., K. M. Tyo, S. Stocke, M. Y. Mahmoud, A. Ramasubramanian, and J. M. Steinbach-Rankins, "Surface-Modified Melphalan Nanoparticles for Intravitreal Chemotherapy of Retinoblastoma", Journal of Investigative ophthalmology & visual science, vol. 60 , issue (5), pp. 1696-1705, 2019.
Mahmoud, M. Y., D. R. Demuth, and D. R. Demuth, "Functional assessment of peptide-modified PLGA nanoparticles against oral biofilms in a murine model of periodontitis", Journal of controlled release, vol. 297, pp. 3-13, 2019.
Abdelaleem, M. Y., M. S. Mowad, E. A. Mohamed, and O. S. El-Tawil, "Cytotoxicity of Silver Nanoparticles (AgNps) in Freshly Prepared Isolated Rat Hepatocytes", Life Sci J, vol. 12, issue (1), pp. 94-103, 2015.
Mahmoud, M. Y., D. R. Demuth, and J. M. Steinbach-Rankins, "BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis-Streptococcus gordonii biofilms.", Journal of nanobiotechnology, vol. 16, issue 1, pp. 69, 2018. Abstract

BACKGROUND: Porphyromonas gingivalis adherence to oral streptococci is a key point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe 10:423-425, 2011). Previous work in our groups has shown that a region of the streptococcal antigen denoted BAR (SspB Adherence Region) inhibits P. gingivalis/S. gordonii interaction and biofilm formation both in vitro and in a mouse model of periodontitis (Daep et al. in Infect Immun 74:5756-5762, 2006; Daep et al. in Infect immun 76:3273-3280, 2008; Daep et al. in Infect Immun 79:67-74, 2011). However, high localized concentration and prolonged exposure are needed for BAR to be an effective therapeutic in the oral cavity.

METHODS: To address these challenges, we fabricated poly(lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol PLGA (mPEG-PLGA) nanoparticles (NPs) that encapsulate BAR peptide, and assessed the potency of BAR-encapsulated NPs to inhibit and disrupt in vitro two-species biofilms. In addition, the kinetics of BAR-encapsulated NPs were compared after different durations of exposure in a two-species biofilm model, against previously evaluated BAR-modified NPs and free BAR.

RESULTS: BAR-encapsulated PLGA and mPEG-PLGA NPs potently inhibited biofilm formation (IC50 = 0.7 μM) and also disrupted established biofilms (IC50 = 1.3 μM) in a dose-dependent manner. In addition, BAR released during the first 2 h of administration potently inhibits biofilm formation, while a longer duration of 3 h is required to disrupt pre-existing biofilms.

CONCLUSIONS: These results suggest that BAR-encapsulated NPs provide a potent platform to inhibit (prevent) and disrupt (treat) P. gingivalis/S. gordonii biofilms, relative to free BAR.

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