Development of Novel PHBV/PCL and BCP Composite for Musculoskeletal Infection: an In Vitro Vancomycin Release and Anti-MRSA Effect

Abstract

Purpose

Antibiotic-loaded polymethylmethacrylate has been conventionally used for osteomyelitis treatment, but it requires a second operation for removal. This study aimed to develop and examine the properties of a novel vancomycin-loaded composite fabricated from biodegradable poly(ε-caprolactone)/poly(hydroxybutyrate-co-hydroxyvalerate)/biphasic calcium phosphate (PCL/PHBV/BCP) for chronic methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.

Materials and methods

The drug-loaded composite was developed using a solvent casting method and fabricated into four formulations: FV1, FV2, FV3, and FV4. The physicochemical characteristics and osteoblast biocompatibility were evaluated. In addition, the drug-release profile and anti-MRSA activity were examined.

Results

Vancomycin conserved its antibiotic property and did not form any interactions with the raw materials. A loading efficiency of more than 80 % was achieved with all formulations. FV2, FV3, and FV4 demonstrated cumulative release of more than 90 % over a couple of months. The bactericidal property was assessed to confirm the efficacy of the released vancomycin, and all composites showed antibacterial effects over 28 days. The release kinetics were best-fitted with the Korsmeyer–Peppas model, and Fickian diffusion was the main transport mechanism. A cytotoxicity test was also performed, and all formulations showed more than 80 % osteoblast viability.

Conclusions

All of the present in vitro results indicated the effectiveness of the new materials as local vancomycin carriers. In vivo animal models should be evaluated to confirm the efficacy for use in humans in the future.

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Abbreviations

MRSA:

Methicillin-resistant Staphylococcus aureus

PMMA:

Polymethylmethacrylate

HA:

Hydroxyapatite

β-TCP:

β-Tricalcium phosphate

BCP:

Biphasic calcium phosphate

PLA:

Poly(lactide)

PGA:

Poly(glycolide)

PCL:

Poly(ε-caprolactone)

PHAs:

Polyhydroxyalkanoates

PHBV:

Poly(hydroxybutyrate-co-hydroxyvalerate)

SEM:

Scanning electron microscopy

XRD:

X-ray diffraction pattern

FTIR:

Fourier transformed infrared

MTT:

(3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide), methyl thiotetrazole

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Acknowledgments

This work was supported by the Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand, under grant EC 522821142. The authors would like to thank Dr. Naruporn Monmaturapot from MTEC, Thailand, for the BCP syntheses and Assoc. Prof. Dr. Chitchamai Ovartlanporn, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Thailand, for the chemical analyses.

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Correspondence to Nisalak Upho.

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Upho, N., Tangtrakulwanich, B., Pripatnanont, P. et al. Development of Novel PHBV/PCL and BCP Composite for Musculoskeletal Infection: an In Vitro Vancomycin Release and Anti-MRSA Effect. J Pharm Innov 10, 211–221 (2015). https://doi.org/10.1007/s12247-015-9219-4

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Keywords

  • Vancomycin
  • In vitro drug release
  • Physicochemical characteristics
  • PHBV/PCL and BCP composite
  • MRSA osteomyelitis