Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal drug delivery.
Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal drug delivery.
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DOI：
10.2147/ijn.s62599
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发表时间：
2014
影响因子：
8
通讯作者：
Guterres SS
中科院分区：
文献类型：
--
作者：
Frank LA;Sandri G;D'Autilia F;Contri RV;Bonferoni MC;Caramella C;Frank AG;Pohlmann AR;Guterres SS
阴道给药途径是实现局部或全身药理作用的多种治疗方法的一种替代选择。然而，药物在该途径中的滞留是制剂研发面临的一个挑战，而使用纳米包封和壳聚糖凝胶可以克服这一挑战。因此，本研究旨在评估含有阳离子和阴离子丙烯酸基纳米胶囊（分别为Eudragit® RS 100和Eudragit® S 100）且以尼罗红作为亲脂性物质模型的壳聚糖水凝胶在阴道给药途径中的性能，通过测量这些制剂的滞留时间和渗透情况来进行评估。制备了几种壳聚糖浓度逐渐增加的制剂，并对其pH值和流变行为进行了分析，以便选择最合适的制剂。评估了这些制剂应用于猪阴道黏膜时黏附（拉伸应力测试和可清洗性曲线）和渗透（共聚焦激光扫描显微镜以及提取后定量）性能的增强情况。所制备的纳米胶囊悬浮液具有适当的特性：尺寸约为200 nm（多分散指数≤0.2）；阳离子制剂的ζ电位约为+10 mV，阴离子制剂的约为 -10 mV；pH值分别为6.1±0.1（Eudragit RS 100）、5.3±0.2（Eudragit S 100）、6.2±0.1（负载尼罗红的Eudragit RS 100）和5.1±0.1（负载尼罗红的Eudragit S 100）。壳聚糖制剂具有适合阴道应用的黏度和酸性pH值（约4.5）。拉伸应力测试表明，与不含纳米胶囊的制剂相比，两种含有聚合物纳米胶囊的制剂都表现出更高的黏膜黏附性。在可清洗性实验中，各制剂之间未发现显著差异。从黏膜提取后进行的共聚焦显微镜观察和荧光定量分析表明，尼罗红被纳米包封时，尤其是在阳离子纳米胶囊中，其渗透更高。基于含2.5%（重量/重量）聚合物纳米胶囊（尤其是阳离子纳米胶囊）的壳聚糖凝胶载体开发的制剂，证明了其对疏水性物质阴道给药的适用性。
The vaginal route of administration is an alternative for several treatments for either local or systemic pharmacological effects. However, the permanence of a drug in this route represents a challenge for formulation development that can be overcome by using nanoencapsulation and chitosan gel. Thus, this work aimed to evaluate the performance of chitosan hydrogels containing cationic and anionic acrylic-based nanocapsules (Eudragit® RS 100 and Eudragit® S 100, respectively) with Nile red as a model of lipophilic substance in the vaginal route of administration, as measured by increases in the residence time and the penetration of these formulations. Several formulations were prepared with increasing chitosan concentrations, and were analyzed in terms of pH and rheological behavior so that the most suitable formulation could be selected. The enhancement of the adhesion (tensile stress test and washability profile) and penetration (confocal laser scanning microscopy and extraction followed by quantification) properties of the formulations, when applied to porcine vaginal mucosa, were evaluated. The nanocapsule suspensions produced presented adequate properties: size of approximately 200 nm (polydispersity index of ≤v0.2); zeta potential around +10 mV for the cationic formulation and -10 mV for the anionic formulation; and pH values of 6.1±0.1 (Eudragit RS 100), 5.3±0.2 (Eudragit S 100), 6.2±0.1 (Nile red loaded Eudragit RS 100), and 5.1±0.1 (Nile red loaded Eudragit S 100). The chitosan formulation presented suitable viscosity for vaginal application and acidic pH (approximately 4.5). The tensile stress test showed that both formulations containing polymeric nanocapsules presented higher mucoadhesion when compared with the formulation without nanocapsules. In the washability experiment, no significant differences were found between formulations. Confocal microscopy and fluorescence quantification after extraction from the mucosa showed higher penetration of Nile red when it was nanoencapsulated, particularly in cationic nanocapsules. The formulations developed based on chitosan gel vehicle at 2.5% weight/weight containing polymeric nanocapsules, especially the cationic nanocapsules, demonstrated applicability for the vaginal delivery of hydrophobic substances.