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Controlled release of antibiotic from surface modified coralline hydroxyapatite.

A suitable method was developed to enhance the use of coralline hydroxyapatite (CHA) as carrier in drug delivery systems. CHA was surface modified by grafting with glycidylmethacrylate using redox initiators. FT-IR spectroscopy and X-ray diffraction were employed for the proof of grafting and phase purity of the graft copolymer. An antibiotic agent, gentamicin, was incorporated into unmodified CHA (UCHA) and surface modified CHA (SCHA). The percentage of loading and release profiles of gentamicin for UCHA and SCHA were evaluated and compared. It was found that the SCHA exhibited higher loading efficiency for gentamicin than the UCHA. In-vitro release profile of gentamicin was assayed by elution in phosphate buffered saline of pH 7.4 at 37[degrees]C. The in-vitro release of gentamicin from SCHA occurred up to 12 days, whereas it was 9 days for UCHA, for the release of most of the gentamicin incorporated. This prolonged release of gentamicin from SCHA was attributed to more interaction between the amino groups of gentamicin and epoxy groups. The results suggest that the SCHA coupled with gentamicin could serve as an effective method of administrating local chemotherapy primarily when used as a strut graft for bone defects.

INTRODUCTION

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 [1]. However, the beads do not bond to living bone, and its toxicity poses a practical clinical problem [2]. Recently, DDS using resorbable biomaterials such as collagen [3], fibrinogen [4], and polylactic acid [5] 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 [12]. 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 [12]. 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]

CONCLUSIONS

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.

Acknowledgement

The author (R.M.) would like to acknowledge CSIR, Government of India for the financial support.

REFERENCES

[1.] Whaling H et al., J. Bone Joint Surg. (Br), 60-B, 270 (1978).

[2.] Petty W et al., Jt. Surg. Am., 60-A, 752 (1978).

[3.] Itokazu M et al., Clin. Mater., 17, 173 (1994).

[4.] Zilch H et al., Arch. Orthop. Trauma Surg., 106, 36 (1986).

[5.] Wei G et al., J. Bone Joint Surg. (Br), 73-B, 246 (1991).

[6.] Jarcho M, Clin. Orthop. Rel. Res. 157, 259 (1981).

[7.] de Groot K, Bioceramics consisting of calcium phosphate, CRC press, Boca Raton, Florida, 1983).

[8.] Ono K et al., Biomaterials, 11, 265 (1990).

[9.] Tung IC, Artif.Cells Blood Substit. Immobil. Biotech, 23, 81 (1995).

[10.] Kano S et al., Biomed. Mater. Eng, 4, 283 (1994).

[11.] Bajpai PK, J. Biomed. Mater. Res, 22, 1245 (1988).

[12.] Sivakumar M. et al., Biomater., 17, 1709 (1996).

R. Murugan and K. Panduranga Rao

Biomaterials Laboratory

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
Geographic Code:9INDI
Date:Jul 1, 2002
Words:1120
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