Department of Mechanical Engineering , University College London , Torrington Place , London WC1E 7JE , U.K.
School of Pharmacy , University College London , 29-39 Brunswick Square , London WC1N 1AX , U.K.
ACS Appl Mater Interfaces. 2018 Apr 25;10(16):13381-13389. doi: 10.1021/acsami.8b03329. Epub 2018 Apr 10.
Mucoadhesive delivery systems have attracted remarkable interest recently, especially for their potential to prolong dosage form resident times at sites of application such as the vagina or nasal cavity, thereby improving convenience and compliance as a result of less frequent dosage. Mucoadhesive capabilities need to be routinely quantified during the development of these systems. This is however logistically challenging due to difficulties in obtaining and preparing viable mucosa tissues for experiments. Utilizing artificial membranes as a suitable alternative for quicker and easier analyses of mucoadhesion of these systems is currently being explored. In this study, the mucoadhesive interactions between progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content) and either artificial (cellulose acetate) or mucosa membranes are investigated by texture analysis and results across models are compared. Mucoadhesion to artificial membrane was about 10 times that of mucosa, though statistically significant ( p = 0.027) association between the 2 data sets was observed. Furthermore, a hypothesis relating fiber-mucosa interfacial roughness (and unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical mucoadhesion theories, was tested to determine its validity. Points of interaction between the fiber and mucosa membrane were examined using atomic force microscopy (AFM) to determine the depths of interpenetration and unfilled voids/roughness, features crucial to mucoadhesion according to the diffusion and mechanical theories of mucoadhesion. A Kendall's tau and Goodman-Kruskal's gamma tests established a monotonic relationship between detaching forces and roughness, significant with p-values of 0.014 and 0.027, respectively. A similar relationship between CMC concentration and interfacial roughness was also confirmed. We conclude that AFM analysis of surface geometry following mucoadhesion can be explored for quantifying mucoadhesion as data from interfacial images correlates significantly with corresponding detaching forces, a well-established function of mucoadhesion.
最近，黏膜黏附给药系统引起了人们的极大兴趣，特别是因为它们有可能延长阴道或鼻腔等应用部位的剂型驻留时间，从而通过减少给药频率提高便利性和顺应性。在开发这些系统时，需要常规量化黏膜黏附能力。然而，由于难以获得和准备用于实验的可行黏膜组织，这在后勤上具有挑战性。目前正在探索利用人造膜作为更快、更容易分析这些系统黏膜黏附的合适替代品。在这项研究中，通过纹理分析研究了载有孕酮的纤维（具有不同的羧甲基纤维素（CMC）含量）与人工（醋酸纤维素）或黏膜膜之间的黏膜黏附相互作用，并比较了不同模型的结果。尽管人工膜的黏膜黏附力约为黏膜的 10 倍，但观察到两组数据之间存在统计学上显著的关联（p = 0.027）。此外，还测试了一个与纤维-黏膜界面粗糙度（以及黏膜上未填充的空隙）与黏膜黏附相关的假设，该假设源自一些经典的黏膜黏附理论，以确定其有效性。使用原子力显微镜（AFM）检查纤维与黏膜膜之间的相互作用点，以确定相互渗透的深度和未填充的空隙/粗糙度，根据黏膜黏附的扩散和机械理论，这些特征对于黏膜黏附至关重要。Kendall 的 tau 和 Goodman-Kruskal 的 gamma 检验分别建立了脱附力与粗糙度之间的单调关系，p 值分别为 0.014 和 0.027，具有统计学意义。还证实了 CMC 浓度与界面粗糙度之间的类似关系。我们得出结论，黏膜黏附后表面几何形状的 AFM 分析可用于量化黏膜黏附，因为界面图像的数据与相应的脱附力显著相关，而脱附力是黏膜黏附的一个公认功能。
