RESUMEN
OBJECTIVE: To develop zoledronic acid (ZA)-loaded collagen membranes, and to study its effect on osteoclast and osteoblast so as to investigate whether ZA-loaded membranes can inhibit local bone resorption and promote bone formation. METHODS: ZA-loaded double-layer (Bio-Gide(®)) and single-layer (BME-10X(®)) collagen membranes were prepared and divided into eight groups according to the concentrations of ZA in the membrane, namely Group BG0, BG1, BG2, BG3 and BM0, BM1, BM2, BM3 (BG refers to Bio-Gide(®), BM refers to BME-10X(®), 0, 1, 2, 3 refer to the concentrations of ZA, 0, 1 × 10(-4), 1 × 10(-3), 1 × 10(-2) mol/L respectively). Blank control group was set without using collagen membrane. The effects of ZA-loaded membranes on osteoclast and osteoblast were assessed using in vitro cell culture models. RESULTS: In vitro coculture of ZA-loaded membrane with osteoclast for seven days showed that the percentage of bone resorption area in BG1, BG2, BG3, BM1, BM2, BM3 were 18.80%, 14.75%, 14.28%, 20.51%, 15.77%, 15.12% respectively, which were lower than that in BG0 (31.53%) and BM0 (32.22%, P < 0.05), and the higher ZA loading was, the stronger its inhibition to osteoclast was. In vitro coculture of ZA-loaded membrane with osteoblast for four days indicated that alkaline phosphatase (ALP) activities in BG2 (154.67 U/g), BM2 (154.33 U/g), BG3 (155.33 U/g), BM3 (152.00 U/g) were higher than that in BG0 (129.33 U/g) and BM0 (127.67 U/g, P < 0.05). What's more, results from seven-day coculture showed that proliferation index in BG2 (7.00) was higher than that in BG0 (6.90). CONCLUSIONS: ZA-loaded collagen membrane can not only inhibit osteoclastic bone resorption but also improve proliferation of osteoblast.
Asunto(s)
Resorción Ósea/patología , Proliferación Celular/efectos de los fármacos , Colágeno/farmacología , Difosfonatos/farmacología , Imidazoles/farmacología , Osteoblastos , Osteoclastos , Fosfatasa Alcalina/metabolismo , Animales , Materiales Biocompatibles/farmacología , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacología , Células Cultivadas , Difosfonatos/administración & dosificación , Relación Dosis-Respuesta a Droga , Imidazoles/administración & dosificación , Membranas Artificiales , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/enzimología , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteogénesis , Conejos , Ácido ZoledrónicoRESUMEN
OBJECTIVE: To develop a new local delivery system, osteoclastic-inhibitor-loaded collagen membrane, and to evaluate its drug loading and drug release properties. METHODS: Efforts were made to develop the drug-loaded membranes by combining two commercially available collagen barrier membranes (Bio-Gide and BME-10X) with zoledronic acid (ZA). The physicochemical and pharmacological properties of resulting materials were determined using SEM, EDS, FTIR, and HPLC. RESULTS: After ZA loading, the micropores between the thin collagen fibers in the Bio-Gide disappeared, whereas crystalloid powders appeared on the surface of pore walls in BME-10X. Phosphorus was detected on both drug-loaded membranes. The Amides shifted. With the same drug solution, Bio-Gide presented larger amount of ZA loading and slower ZA release than BME-10X. ZA loading did not affect the 3D fiber network and the degradation of membranes. CONCLUSION: Both collagen membranes load ZA successfully and delay drug release. But Bio-Gide shows higher loading values and slower release than BME-10X.