Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer^® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen’s egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

Graphical Abstract

中文翻译：

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壳聚糖包覆的载姜黄素脂质核纳米胶囊热敏黏膜粘附水凝胶治疗口腔鳞状细胞癌

可以选择口腔给药作为治疗各种疾病的局部或全身作用的药物途径。本研究提出开发一种热敏水凝胶，其中含有负载姜黄素的脂质核纳米胶囊，并涂有壳聚糖，以增加粘膜粘附，从而规避这种给药途径的一些局限性。羟丙基甲基纤维素和泊洛沙姆^®407 被合并用于水凝胶生产。分析了物理化学表征参数，例如粒度分布、平均直径、多分散指数、zeta 电位和形态。获得平均直径为 173 ± 22 nm 的球形均匀颗粒，LNCc（姜黄素脂质核心纳米胶囊）和 CLNCc（壳聚糖-姜黄素脂质核心纳米胶囊）为 179 ± 48 nm。LNCc 的 PDI 等于 0.09 ± 0.02，CLNCc 的 PDI 等于 0.26 ± 0.01，证实了同质性。猪口腔粘膜的拉伸分析和可洗性测试表明，与悬浮的纳米胶囊相比，水凝胶的粘膜粘附性更高，在粘膜上保留长达 8 小时（10.92 ± 3.95 µg 姜黄素用于 H-LNCc 洗涤，28.41 ± 24.47 µg 用于 H -CLNCc) 与后者相比，后者仅在膜上清洗 90 分钟 (62. LNCc 为 60 ± 4.72 µg，CLNCc 为 52.08 ± 1.63 µg）。通过鸡蛋绒毛尿囊膜试验 (HET-CAM) 评估了制剂的潜在刺激性 (IR)，未观察到刺激现象。在体外模型中测试了制剂对口腔鳞状癌细胞系的功效，显示所有测试组的细胞活力显着降低。这些发现表明，所提出的纳米系统具有粘膜粘附性，并具有提供口腔治疗的潜力。显示所有测试组的细胞活力显着降低。这些发现表明，所提出的纳米系统具有粘膜粘附性，并具有提供口腔治疗的潜力。显示所有测试组的细胞活力显着降低。这些发现表明，所提出的纳米系统具有粘膜粘附性，并具有提供口腔治疗的潜力。

图形概要