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Physicochemical and In Vitro Evaluation of Drug Delivery of an Antibacterial Synthetic Benzophenone in Biodegradable PLGA Nanoparticles

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  • Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems
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Abstract

Due to the increasing incidents of antimicrobial-resistant pathogens, the development of new antibiotics and their efficient formulation for suitable administration is crucial. Currently, one group of promising antimicrobial compounds are the benzophenone tetra-amides which show good activity even against gram-positive, drug-resistant pathogens. These compounds suffer from poor water solubility and bioavailability. It is therefore important to develop dosage forms which can address this disadvantage while also maintaining efficacy and potentially generating long-term exposures to minimize frequent dosing. Biodegradable nanoparticles provide one solution, and we describe here the encapsulation of the experimental benzophenone-based antibiotic, SV7. Poly-lactic-co-glycolic-acid (PLGA) nanoparticles were optimized for their physicochemical properties, their encapsulation efficiency, sustained drug release as well as antimicrobial activity. The optimized formulation contained particles smaller than 200 nm with a slightly negative zeta potential which released 39% of their drug load over 30 days. This formulation maintains the antibacterial activity of SV7 while minimizing the impact on mammalian cells.

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Acknowledgments

OMM acknowledges the Wayne State University Start-Up grant and Innovation Fellowship grant. SMF acknowledges NIH grant R01AI109139 for support. GC acknowledges UniNa and Compagnia San Paolo in the frame of Programme STAR (CALL 2016). The Electron Microscopy Core Facility at Wayne State University is partially supported by NSF-MRI grant 0216084 and NSF-MRI grant 0922912. We are grateful to Dr. Zhi Mei for expert support with the SEM imaging of our samples.

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Authors and Affiliations

  1. Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig-Maximilians-University, 81337, Munich, Germany

    Gabriella Costabile & Olivia M. Merkel

  2. Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, 48201, USA

    Kathrin I. Gasteyer, Venkatereddy Nadithe, Katherine Van Denburgh, Qian Lin, Shiv Sharma, Steven M. Firestine & Olivia M. Merkel

  3. Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, 57007, USA

    Joshua J. Reineke

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  1. Gabriella Costabile
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Correspondence to Olivia M. Merkel.

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Guest Editors: Mahavir Bhupal Chougule, Vijaykumar B. Sutariya and Sudip K. Das

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Costabile, G., Gasteyer, K.I., Nadithe, V. et al. Physicochemical and In Vitro Evaluation of Drug Delivery of an Antibacterial Synthetic Benzophenone in Biodegradable PLGA Nanoparticles. AAPS PharmSciTech 19, 3561–3570 (2018). https://doi.org/10.1208/s12249-018-1187-9

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  • DOI: https://doi.org/10.1208/s12249-018-1187-9

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