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Issue 5, 2017

Biodegradable nitric oxide precursor-loaded micro- and nanoparticles for the treatment of Staphylococcus aureus biofilms

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Abstract

Bacteria in biofilms are more difficult to eradicate than planktonic bacteria and result in treatment challenges for many chronic infectious diseases. Nitric oxide (NO) is an endogenous molecule that offers potential as an alternative to conventional antibiotics; however its sustained topical delivery to biofilms is not readily achieved. With this in mind, we report the development of biodegradable poly(lactide-co-glycolide) (PLGA) based microparticles (MP) and nanoparticles (NP) for encapsulation of the NO precursor isosorbide mononitrate (ISMN) and the controlled delivery to Staphylococcus aureus (S. aureus) biofilms. Firstly, water-in-oil-in-water (w/o/w) emulsification/solvent evaporation methods for PLGA NP and MP syntheses were experimentally optimised with respect to particle size and ISMN loading/encapsulation efficiency. The influence of various experiment parameters, such as the volume of inner aqueous phase, concentration of surfactants, mixing time on the particle size, drug loading and encapsulation efficiency were investigated systematically. Both PLGA MP and NP formulations enabled sustained ISMN release in physiological media over 3 to 5 days. PLGA MP with diameters of ∼3 μm and ISMN loading of 2.2% (w/w) were identified as the optimum delivery system and demonstrated significant antibacterial activity in S. aureus biofilms. This behaviour is considered to be due to targeted biofilm delivery through a combination of effective penetration and sustained release of ISMN.

Graphical abstract: Biodegradable nitric oxide precursor-loaded micro- and nanoparticles for the treatment of Staphylococcus aureus biofilms

Article information


Submitted
19 Dec 2016
Accepted
03 Jan 2017
First published
09 Jan 2017

This article is Open Access

J. Mater. Chem. B, 2017,5, 1005-1014
Article type
Paper

Biodegradable nitric oxide precursor-loaded micro- and nanoparticles for the treatment of Staphylococcus aureus biofilms

S. Hasan, N. Thomas, B. Thierry and C. A. Prestidge, J. Mater. Chem. B, 2017, 5, 1005 DOI: 10.1039/C6TB03290G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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