Elsevier

Biomaterials

Volume 22, Issue 7, April 2001, Pages 701-708
Biomaterials

Bioactivity in glass/PMMA composites used as drug delivery system

https://doi.org/10.1016/S0142-9612(00)00233-7Get rights and content

Abstract

Gentamicin sulfate has been incorporated in composites prepared from a SiO2–CaO–P2O5 bioactive glass and polymethylmethacrylate. Data showed that these materials could be used as drug delivery system, keeping the bioactive behavior of the glass. The composites supply high doses of the antibiotic during the first hours when they are soaked in simulated body fluid (SBF). Thereafter, a slower drug release is produced, supplying ‘maintenance’ doses until the end of the experiment. The gentamicin release rate is related with the ionic Ca2+ and H3O+ exchange between composite and SBF. The porous structure of the composites allows the growth of hydroxycarbonate apatite on the surface and into the pores.

Introduction

The study of biomaterials suitable to be used as filling bone are one of the most interesting fields in orthopedic surgery [1], [2], [3]. These materials are needed to fill the defects of dead spaces caused by surgical intervention over traumatized or damaged bone. Porous apatites, β-TCP, biphasic ceramics (OHAp-β-TCP) and bioactive glasses are often used, due to their excellent biocompatibility and integration with the osseous tissue [4], [5], [6], [7].

An important trouble associated with the use of materials for bone-filling is the osteomielitis incidence. Techniques for its treatment include the systemic antibiotic administration, surgical debridement, wound drainage, and implant removal is, therefore, essential for the prevention of further complication, such as loss of function and septicemia [8].

Local drug release in the implanted site appears to be a very interesting alternative. The possibility of introducing drug release systems into the implant site has been widely studied and used. Beads of PMMA containing gentamicin has been one of the first systems used [9], [10]. Later, alternative systems such as biodegradable materials [11], bioceramics [12] or ceramic/polymer composites [13] were developed. Antibiotics [14], [15], [16], growth factor and hormones [17], [18], [19], chemiotherapeutic agents [12], antistrogens [20], antiinflammatory drugs [21], [22], [23], etc., have been introduced into the systems mentioned above.

The bibliography shows that the systems developed for drug release have been very numerous. However, there have been only a few studies about filling bone materials showing simultaneously controlled drug release and bioactive behaviour [24]. Actually, it seems to be a very attractive idea to look for materials that could release an antibiotic in a local and controlled way while showing bioactive properties. These materials would prevent infections and also would ensure the bone integration and regeneration.

In this work we have synthesized glass/acrylic cement composites, and gentamicin sulfate has been added. These materials are formed by a discrete phase (glass) and a continuous phase (PMMA) in which gentamicin is included. The PMMA hydrophobicity should avoid the instantaneous gentamicin release from the composite to the environment, while the glass should supply the bioactive behaviour and release adequate doses of gentamicin during the first hours after implantation. These composites, made up of these components, can represent an advantageous solution to solve problems of bone filling as well as bone regeneration.

Section snippets

Experimental

The glass was prepared by hydrolysis and polycondensation of tetraethyl orthosilicate (TEOS), triethyl phosphate (TEP) and Ca(NO3)2·4H2O to obtain a nominal composition (mol%) of SiO2 (58), CaO (36) and P2O5 (6) as it is described by Vallet-Regı́ et al. [25]. The stabilization treatment was carried out by means of heating the dried gel at 700°C for 3 h. The stabilized glass was ground and sieved, selecting the fraction from 32 to 63 μm. Particle size and particle size distribution were determined

Results

Fig. 1 shows one of the thermograms obtained for the composite. All thermograms showed an important mass loss between 240 and 400°C due to the decomposition of gentamicin sulfate and PMMA. From 400 to 570°C the mass loss is lower, remaining stable from 570°C until final temperature. At the end of the analysis, a mass percentage of 52–55% corresponding to the glass of the composite was observed in all the experiments.

Differential thermal analysis (DTA) showed an endothermic process at 244°C

Discussion

The gentamicin concentration data in SBF as a function of soaking time shows that drug release is produced fundamentally in a first stage, in which after 48 h 80% of gentamicin is released. Subsequently, the release rate decreases and after 14 days, 90% of the drug load is present in the SBF.

EDS and TG/DTA analyses confirm the process of gentamicin release after 14 days in SBF. EDS spectra obtained after 7 days of soaking do not show the line corresponding to sulfur. On the other hand, DTA

Conclusions

(1)Glass/polymer/gentamicin composites suitable to be used as biomaterials have been synthesized.
(2)The composites supply high doses of the antibiotic during the first hours when soaked in SBF. Thereafter, a slower drug release is produced, supplying a ‘maintenance’ doses until the end of the experiment. The gentamicin release rate is related with the ionic Ca2+ and H3O+ exchange between composite and SBF.
(3)Nanocrystalline HCA grows on the composite surface when it is in contact with SBF. The

Acknowledgements

Financial support of CICYT, Spain, through research projects MAT98-0746C02-01 and MAT99-0466 is acknowledged. We also thank A. Rodrı́guez (Electron Microscopy Center, Complutense University), and F. Conde (C.A.I. X-ray Diffraction, Complutense University) for valuable technical and professional assistance. B. Braun Medical SA kindly supplied gentamicin sulfate.

References (30)

  • L.L. Hench

    Bioceramicsfrom concept to clinic

    J Am Ceram Soc

    (1991)
  • H.W. Bucholz et al.

    Infected prosthesesthe role of antibiotic cement

  • H. Wahlig et al.

    The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study

    J Bone Jt Surg Br

    (1978)
  • V. Vecsei et al.

    Treatment of chronic osteomyelitis by necrectomy and gentamicin–PMMA beads

    Clin Orthop

    (1981)
  • M.F. Yagmurlu et al.

    Sulbactam-cefoperazone polyhydroxybutarate-co-hydroxyvalerate (PHBV) local antibiotic delivery systemin vivo effectiveness and biocompatibility in the treatment of implant-related experimental osteomyelitis

    J Biomed Mater Res

    (1999)
  • Cited by (120)

    • Biomatériaux et ostéoradionécrose mandibulaire: revue de la littérature selon la méthodologie SWiM

      2022, Annales Francaises d'Oto-Rhino-Laryngologie et de Pathologie Cervico-Faciale
    • Hierarchically multifunctional bioactive nanoglass for integrated tumor/infection therapy and impaired wound repair

      2022, Materials Today
      Citation Excerpt :

      Due to its high osteogenic biological activity, gene activation ability and controllable biodegradability, it is widely used for tissue repair and regeneration in clinical practice [8–10]. The high specific surface area and nanoscale size make bioactive glass nanoparticles (BGN) a promising candidate for promoting bone regeneration or tumor therapy [11,12]. In recent years, the main researchers including our group have designed various multifunctional BGNs for enhanced tissue repair, drug/gene delivery, bioimaging and tumor therapy [13–17].

    View all citing articles on Scopus
    View full text