Prevention of Biofilm Formation by Methacrylate-Based Copolymer Films Loaded With Rifampin, Clarithromycin, Doxycycline Alone or in Combination

Abstract

Purpose

This study reports the incorporation of the antibiotics rifampin, doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and their effect on biofilm prevention.

Background

Invasive procedures in patients such as surgical device, or intravenous or urinary catheter implantation, often results in complicated hospital-acquired nosocomial infections. Biofilm formation is essential to establish these infections on these devices and novel antibiotic delivery approaches are needed for more effective management.

Methods

The films were evaluated in vitro for drug release and for their ability to prevent biofilm formation by methicillin susceptible and methicillin resistant Staphylococcus aureus. Surface tension components, obtained from contact angle measurements, and the morphology of the films evaluated by scanning electron microscopy were also investigated.

Results

In this study, antibiotic-loaded methacrylic copolymer films that effectively released rifampin, clarithromycin and doxycycline for up to 21 days prevented biofilm formation when tested in an in vitro bioreactor model. These drug loaded copolymer films provided the advantage by coating materials with a novel surface that was unsuitable for resettling of biofilms once the antibiotic was dissolved from the polymer surface. A combination of rifampin and clarithromycin released from the polymer film provided >99.9% kill of an MRSA inoculate for up to 72 h.

Conclusion

Results showed that combining multiple drugs in copolymer films with unique surface properties, initial hydrophilicity and increase in roughness, can be an effective way to prevent biofilm formation.

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Abbreviations

CLR:

Clarithromycin

DIM:

Diiodomethane

DOX:

Doxycycline

EG:

Ethylene glycol

GPC-MALLS-RI:

Gel permeation chromatography coupled to multi-angle laser light scattering and refractive index double detection

HQ:

Hydroquinone

KPS:

Potassium persulphate

MMA:

Methyl methacrylate

MRSA:

Methicillin-resistant Staphylococcus aureus

MSSA:

Methicillin-susceptible Staphylococcus aureus

Poly(S-co-MMA):

Poly(styrene-co-methyl methacrylate)

RIF:

Rifampicin

S:

Styrene

SDS:

Sodium dodecyl sulphate

W A :

Work of adhesion

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Correspondence to Melgardt M. de Villiers.

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Rose, W.E., Otto, D.P., Aucamp, M.E. et al. Prevention of Biofilm Formation by Methacrylate-Based Copolymer Films Loaded With Rifampin, Clarithromycin, Doxycycline Alone or in Combination. Pharm Res 32, 61–73 (2015). https://doi.org/10.1007/s11095-014-1444-x

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KEY WORDS

  • antibiotic
  • biofilm
  • drip flow bioreactor
  • methacrylate copolymer coating