Gomez C, Blanco M D, Bernardo M V, Sastre R L, Teijón J M
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
J Pharm Pharmacol. 1998 Jul;50(7):703-12. doi: 10.1111/j.2042-7158.1998.tb07130.x.
This study has tested the application of three different copolymeric poly(acrylamide-co-monoethyl itaconate; A/MEI) hydrogels, 90A/10MEI, 75A/25MEI and 60A/40MEI, on the release of cytarabine (ara-C). The drug was incorporated in gels by placing it in the polymerization feed mixture and discs loaded with 5-50 mg ara-C were obtained. The amount of swelling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 and 82% w/w, depending on the composition of the copolymer. The diffusion studies followed Fick's second law. The diffusion coefficients for swelling of the gels were between 9.30 x 10(-11) m2 s(-1) and 37.42 x 10(-11) m2 s(-1); those for release of ara-C were between 3.42 x 10(-11) m2 s(-1) and 10.25 x 10(-11) m2 s(-1). The activation energies for swelling were in the range 16.60 +/- 2.59-21.85 +/- 1.78 kJ mol(-1); those for ara-C release were 28.13 +/- 3.1-29.7 +/- 4.6 kJ mo(-1). To determine the applicability of these copolymers, 75A/25MEI gel was subcutaneously implanted in rats and the plasma concentration of the drug was determined by high-performance liquid chromatography. The concentration of ara-C in plasma (range 17.67 +/- 5.68-10.76 +/- 2.15 microg mL(-1)) was maintained during the first stages (2-8 h) and no drug was detected after 32 h. This route of administration was compared with intraperitoneal injection of the drug. In conclusion, ara-C can be incorporated in hydrogels and released in a pharmacologically active form. The concentration of ara-C in plasma is maintained for long enough to improve therapeutic results.
本研究测试了三种不同的共聚聚丙烯酰胺 - 衣康酸单乙酯（A/MEI）水凝胶，即90A/10MEI、75A/25MEI和60A/40MEI，对阿糖胞苷（ara-C）释放的作用。通过将药物置于聚合进料混合物中，使其掺入水凝胶中，从而获得负载有5 - 50mg阿糖胞苷的圆盘。在盐溶液（NaCl，0.9% w/w）中平衡时的溶胀量在78%至82% w/w之间，具体取决于共聚物的组成。扩散研究遵循菲克第二定律。水凝胶溶胀的扩散系数在9.30×10⁻¹¹ m² s⁻¹至37.42×10⁻¹¹ m² s⁻¹之间；阿糖胞苷释放的扩散系数在3.42×10⁻¹¹ m² s⁻¹至10.25×10⁻¹¹ m² s⁻¹之间。溶胀的活化能在16.60±2.59 - 21.85±1.78 kJ mol⁻¹范围内；阿糖胞苷释放的活化能为28.13±3.1 - 29.7±4.6 kJ mo⁻¹。为了确定这些共聚物的适用性，将75A/25MEI水凝胶皮下植入大鼠体内，并通过高效液相色谱法测定药物的血浆浓度。在最初阶段（2 - 8小时），血浆中阿糖胞苷的浓度（范围为17.67±5.68 - 10.76±2.15μg mL⁻¹）得以维持，32小时后未检测到药物。将这种给药途径与药物的腹腔注射进行了比较。总之，阿糖胞苷可以掺入水凝胶中，并以药理活性形式释放。血浆中阿糖胞苷的浓度能维持足够长的时间以改善治疗效果。
