Bioactivity in glass/PMMA composites used as drug delivery system
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.
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