Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid (UCM), Madrid, Spain.
Pharm Res. 2012 Aug;29(8):2329-40. doi: 10.1007/s11095-012-0761-1. Epub 2012 May 8.
Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration.
The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM).
While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH(2)(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)>> CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %).
The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and dendrimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability.
开发基于生物传感器芯片技术的首个体外方法，旨在探测跨膜眼部粘蛋白与用于眼部给药的粘性聚合物和树枝状聚合物之间的界面相互作用现象。
使用表面等离子体共振（SPR）技术。在芯片表面制备跨膜眼部粘蛋白表面，并通过 QCM-D（石英晶体微天平与耗散）和 XPS（X 射线光电子能谱）进行表征。测试的粘膜粘附分子为：透明质酸（HA）、羧甲基纤维素（CMC）、羟丙基甲基纤维素（HPMC）、壳聚糖（Ch）和聚酰胺胺树枝状聚合物（PAMAM）。
虽然 Ch 与眼部跨膜粘蛋白起源于界面相互作用，但对于 HA、CMC 和 HPMC，在眼科临床实践中使用的浓度下，链扩散似乎是生物粘附所必需的。有趣的是，无论其表面化学基团如何，PAMAM 树枝状聚合物都与跨膜眼部粘蛋白形成永久性界面相互作用，这表明这些多价系统的协同效应具有重要意义。聚合物与眼部膜相关粘蛋白的界面相互作用顺序如下：Ch（1%）>G4PAMAM-NH2（2%）=G4PAMAM-OH（2%）>G3.5PAMAM-COOH（2%）>>CMC（0.5%）=HA（0.2%）=HPMC（0.3%）。
所提出的方法可用于区分分子水平上粘蛋白-聚合物的化学相互作用。结果增强了壳聚糖和树枝状聚合物作为能够增加药物在眼部表面滞留时间从而提高其生物利用度的聚合物的有用性。
