Controlled release of antibiotic from surface modified coralline hydroxyapatite.
Controlled drug release from delivery systems has been sought as an effective method for the treatment of bone related diseases. Different kinds of drug delivery systems (DDS) have been developed in particular antibiotic loaded polymethylmethacrylate (PMMA) beads, which are widely used . However, the beads do not bond to living bone, and its toxicity poses a practical clinical problem . Recently, DDS using resorbable biomaterials such as collagen , fibrinogen , and polylactic acid  have been developed. These do not require removal, but do not replace bone grafting. Therefore, hydroxyapatite (HA) was selected as the DDS because of its biocompatibility and osteoconductivity [6-8]. The HA have been used clinically as drug carriers and delivery systems for numerous drugs [9-11]. In most of the cases, surface properties of the HA play an important role when in use clinically as its surface is in direct contact with body fluids. Therefore to modify the surface properties of HA is of great importance. Keeping the above points in view, we modified surface properties of coralline hydroxyapatite (CHA), derived from Indian coral, by grafting with glycidylmethacrylate (GMA) using redox initiators and subsequently coupled with gentamicin and characterized for drug loading and in-vitro release characteristics.
MATERIALS AND METHODS
Coralline hydroxyapatite was prepared in our laboratory as reported in elesvier . The surface of CHA was modified by grafting with GMA using potassium persulphate and sodium meta bisulphite as initiators in aqueous medium at room temperature and subsequently coupled with gentamicin through epoxy groups.
Loading of gentamicin into UCHA and SCHA was done in phosphate buffered saline (PBS) of pH 7.4 at 37[degrees]C for 12h. In brief, 50mg of UCHA and SCHA were separately suspended in 5ml of PBS containing 50mg of gentamicin i.e. 10mg/ml. After 12h, the biomaterials were separated by centrifugation and lyophilized. The estimation of gentamicin uptake by the UCHA and SCHA was carried out through an indirect method, by finding the Correspondence to Mr. R. Murugan difference in gentamicin concentration in the loading buffer, before and after loading. The amount of loaded gentamicin was estimated by using UV-spectrophotometer at the optical density of 257nm. In-vitro release of gentamicin from UCHA and SCHA (50mg each) was carried out in 2 ml PBS of pH 7.4 at 37[degrees]C. An aliquot of 2ml was collected at regular intervals and the amount of gentamicin released was measured at 257nm. At each time 2ml of fresh PBS was replaced to maintain a constant volume.
RESULTS AND DISCUSSION
Fig. 1(a, b) show typical IR spectra of UCHA and SCHA respectively. Fig.1a indicated all the characteristic peaks of CHA . Fig. 1b indicated some new peaks in addition of UCHA: >C=O at 1730 [cm.sup.-1], -C-O-at 1260 [cm.sup.-1] and oxirane ring at 853 and 905 [cm.sup.-1], which resulted from the grafting of GMA onto hydroxyl groups of CHA. The XRD patterns of UCHA and SCHA showed identical peaks, Fig. 2(a-b) respectively, and the crystalline nature of the apatite has not changed due to the grafting reaction, which implies that the poly(GMA) were grafted on the surface of CHA.
[FIGURES 1-2 OMITTED]
The percentage of loaded gentamicin was calculated and found to be 31.76 [+ or -] 0.64% and 59.0
8 [+ or -] 2.36% for UCHA and SCHA respectively. The results indicated that the SCHA has taken up higher amounts of gentamicin due to surface modification, as expected, compared to UCHA. Fig. 3 shows in-vitro release profile of gentamicin from UCHA and SCHA. In the case of UCHA, 50% of the loaded gentamicin was released within gentamicin release from SCHA took 6 days. The release time of gentamicin from UCHA (100%) was calculated as 9 days, however it took 12 days for the almost complete release from SCHA. Though similar release pattern for both UCHA and SCHA was observed, the release of gentamicin from SCHA was slowed down after 2 days. The release profile of SCHA exhibited a higher percentage of loading and prolonged release in a near zero order fashion.
[FIGURE 3 OMITTED]
The present investigation demonstrated the possibilities of surface modification of CHA by grafting with GMA using redox initiators in an aqueous medium. The surface modification of CHA has been proved by FT-IR and XRD analysis. In-vitro results of SCHA clearly indicated a higher percentage of loading and prolonged release. This kind of SCHA avoids any post-surgery infection apart from being used as bone repair and regenerative material.
The author (R.M.) would like to acknowledge CSIR, Government of India for the financial support.
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R. Murugan and K. Panduranga Rao
Central Leather Research Institute
Chennai 600 020.
Correspondence to Mr. R. Murugan
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|Author:||Murugan, R.; Rao, K. Panduranga|
|Publication:||Trends in Biomaterials and Artificial Organs|
|Date:||Jul 1, 2002|
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