Cruz Letícia, Schaffazick Scheila R, Dalla Costa Teresa, Soares Leonardo U, Mezzalira Graziela, da Silveira Nádya P, Schapoval Elfrides E S, Pohlmann Adriana R, Guterres Sílvia S
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):3154-62. doi: 10.1166/jnn.2006.417.
Nanocapsules are vesicular drug carriers constituted of an oil core, a polymeric wall, and surfactants. A general understanding about the influence of the polymeric wall of nanocapsules on the release profiles of drugs is not known. So, this work was devoted to characterize formulations prepared without polymer or containing it at different concentrations. The indomethacin ethyl ester was used as model and the strategy was based on its interfacial alkaline hydrolysis simulating a sink condition for the release. The antiedematogenic activity in rats for ester-loaded-nanocarriers was also evaluated. The nanocapsules (NC) and nanoemulsion (NE) presented particle sizes below 300 nm, polydispersity lower than 1.2 and pH around 5. SAXS analyses showed that the sorbitan monostearate is dissolved in the oil and the polymer presents regions of crystallinity independently on the PCL concentration. TEM analyses showed droplets (NE) and spherical particles (NC). The time for the total disappearance of the ester varied from 12 h to 24 h depending on the polymer concentration. The biexponential model showed that the indomethacin ester was essentially entrapped within the nanocarriers in an extension of 85 to 95%. The half-lives varied from 147 to 289 min for the sustained phases and from 3 to 6 min for the burst phases. The ester-loaded-NC showed significant antiedematogenic activity, while the ester-loaded-NE did not inhibit the carrageenin-induced paw edema. The nanocapsules promoted the absorption of the indomethacin ethyl ester and the presence of the polymer is important to achieve the pharmacological effect.
纳米胶囊是由油核、聚合物壁和表面活性剂构成的囊泡状药物载体。目前对于纳米胶囊的聚合物壁对药物释放曲线的影响尚无普遍认识。因此，本研究致力于对不含聚合物或含有不同浓度聚合物的制剂进行表征。以吲哚美辛乙酯作为模型，该策略基于其界面碱性水解，模拟药物释放的漏槽条件。还评估了载酯纳米载体对大鼠的抗水肿活性。纳米胶囊（NC）和纳米乳剂（NE）的粒径均低于300nm，多分散性低于1.2，pH值约为5。小角X射线散射分析表明，单硬脂酸山梨坦溶解在油相中，且聚合物呈现出结晶区域，与聚己内酯浓度无关。透射电镜分析显示出液滴（NE）和球形颗粒（NC）。酯完全消失的时间根据聚合物浓度在12小时至24小时之间变化。双指数模型表明，吲哚美辛酯基本上以85%至95%的比例包封在纳米载体内。持续相的半衰期为147至289分钟，突释相的半衰期为3至6分钟。载酯NC表现出显著的抗水肿活性，而载酯NE并未抑制角叉菜胶诱导的爪肿胀。纳米胶囊促进了吲哚美辛乙酯的吸收，聚合物的存在对于实现药理作用很重要。
