Kwunchit Oungbho

Biocompatability of hydroxyapatite composite as a local drug delivery system

Purpose. To investigate the biocompatibility of hydroxyapatite composite (hydroxyapatite, plaster of Paris, and chitosan) impregnated with gentamicin, fosfomycin, imipenem, or amphotericin B. Methods. The interactions of the extract from each drug against osteoblast were tested using the methylthiotetrazole test. Results. Extracts from all drugs showed good biocompatibility at concentrations varying from 10 μg/ml to 1000 μg/ml. Imipenem and amphotericin B at a concentration of 1000 μg/ml had a significantly higher percentage of cell viability than the control group. No morphological change of osteoblast was observed in all drug tests at any concentrations. Conclusion. The hydroxyapatite composite had a good biocompatibility for carrying gentamicin, fosfomycin, imipenem, or amphotericin B.

The efficacy of hydroxyapatite composite impregnated with amphotericin B.

We investigated the efficacy of local biodegradable composites composed of hydroxyapatite-plaster of paris and either chitosan or alginate binder impregnated with amphotericin B. Antifungal activity was tested for Candida albicans using a modified disc diffusion technique for 6 weeks and compared with similarly impregnated polymethylmethacrylate. The physicochemical properties of each preparation were evaluated using scanning electron microscopy and Fourier transform infrared spectroscopy. The antifungal activity of amphotericin B eluted from the hydroxyapatite composites was significantly greater than the polymethylmethacrylate after 7 days. The hydroxyapatite composites and the polymethylmethacrylate system sustained their antifungal activity for at least 1 month. However, after 5 weeks, the antifungal activities of the polymethylmethacrylate systems rapidly lessened, while the hydroxyapatite composites sustained their activities at a much higher level. We found no difference in antifungal activity between the hydroxyapatite composite using either the chitosan or alginate binder. Scanning electron microscopy and Fourier transform infrared spectroscopy revealed the drug release profile. The hydroxyapatite composites impregnated with amphotericin B showed superior antifungal efficacy over those loaded in polymethylmethacrylate in an in vitro study, but additional in vivo research is needed to confirm this result.

The efficacy of methotrexate-impregnated hydroxyapatite composites on human mammary carcinoma cells.

Purpose. To investigate the efficacy of local biodegradable composites of hydroxyapatite, plaster of Paris, and a binder of either alginate or chitosan impregnated with methotrexate on human mammary carcinoma cells. Methods. An in vitro analysis of drug dissolution and a cytotoxicity test on human mammary carcinoma cells were performed over one month. Physicochemical properties of each composite were investigated using scanning electron microscopy, X-ray diffractometry, and Fourier transform infrared spectroscopy. Results. Both composites with a binder of either alginate or chitosan could release methotrexate for over one month. The amount of methotrexate released depended on the amount of methotrexate loaded. The composite using alginate as a binder released a significantly greater amount of methotrexate than that using chitosan as a binder (p<0.05). The elution of both composites showed favourable cytotoxicity when the concentration was greater than 5 μg/ml. Conclusion. Methotrexate-impregnated hydroxyapatite composites appear to be effective local skeletal methotrexate delivery systems against human mammary carcinoma cells in an in vitro model.

Fabrication of pluronic and methylcellulose for etidronate delivery and their application for osteogenesis

Novel hydrogels were prepared by blending 4% (w/w) methylcellulose (MC) with various concentrations of 12, 14, 16, 18 and 20% (w/w) pluronic F127 (PF) to form injectable implant drug delivery systems. The blends formed gels using lower concentrations of PF compared to when using PF alone. Etidronate sodium (EDS) at a concentration of 4×10(-3)M was loaded into these blends for producing an osteogenesis effect. The pure gels or EDS loaded gels exhibited cytocompatibility to both the osteoblast (MC3T3-E1) and myoblast (C2C12) cell lines whereas the gels of 16PF, 18PF and 20PF were very cytotoxic to the cells. The EDS loaded gels demonstrated significantly greater alkaline phosphatase (ALP) activities compared to the pure gels. The longer exposure time periods of the samples to the cells, the greater was the ALP activity. These EDS loaded gels significantly increased proliferation of both cell lines thus indicating a bone regeneration effect. The PF/MC blends prolonged the in vitro release of EDS for more than 28 days. Based on the in vitro degradation test, the MC extensively improved the gel strength of the PF and delayed the degradation of the gels thus making them more functional for a sustained drug delivery for osteogenesis.