Horvát Gabriella, Gyarmati Benjámin, Berkó Szilvia, Szabó-Révész Piroska, Szilágyi Barnabás Áron, Szilágyi András, Soós Judit, Sandri Giuseppina, Bonferoni Maria Cristina, Rossi Silvia, Ferrari Franca, Caramella Carla, Csányi Erzsébet, Budai-Szűcs Mária
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
Soft Matters Group, Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Budafoki út 8., H-1111 Budapest, Hungary.
Eur J Pharm Sci. 2015 Jan 25;67:1-11. doi: 10.1016/j.ejps.2014.10.013. Epub 2014 Nov 4.
The ophthalmic formulations on the market suffer from poor bioavailability, and it would therefore be useful to design a new formulation which is able to prolong the residence time and reduce the administration frequency. Polymer matrices which exhibit strong mucoadhesion are promising platforms in ocular drug delivery from the aspect of improved bioavailability. In the present study, an in situ gelling, mucoadhesive drug delivery system was fabricated from thiolated poly(aspartic acid) (ThioPASP). The thiol groups of ThioPASP are able to form disulphide linkages with the mucin glycoproteins and prolong the residence time on the eye. The effects of the thiol groups on the structure, swelling behaviour and mucoadhesive character of the gel and on the drug release profile were determined. The gel structure was characterized by means of rheology. The ThioPASP gel was demonstrated by rheology, tensile test and 'wash away' measurements to display strong mucoadhesion. The drug release from the ThioPASP gel was studied on a vertical Franz diffusion cell: a burst release of sodium diclofenac occurred in the first hour, followed by sustained release of the encapsulated drug for up to 24h. The results proved the importance of the presence of the thiol groups and suggested that a ThioPASP formulation can be useful as an in situ gelling, ocular dosage form.
市场上的眼科制剂存在生物利用度差的问题，因此设计一种能够延长停留时间并减少给药频率的新制剂将很有用。从提高生物利用度的角度来看，具有强粘膜粘附性的聚合物基质是眼部药物递送中有前景的平台。在本研究中，由硫醇化聚天冬氨酸（ThioPASP）制备了一种原位凝胶化、粘膜粘附性药物递送系统。ThioPASP的硫醇基团能够与粘蛋白糖蛋白形成二硫键，并延长在眼部的停留时间。测定了硫醇基团对凝胶的结构、溶胀行为和粘膜粘附特性以及药物释放曲线的影响。通过流变学对凝胶结构进行了表征。通过流变学、拉伸试验和“冲洗”测量证明ThioPASP凝胶具有很强的粘膜粘附性。在垂直Franz扩散池上研究了ThioPASP凝胶的药物释放：双氯芬酸钠在第一小时出现突释，随后包封药物持续释放长达24小时。结果证明了硫醇基团存在的重要性，并表明ThioPASP制剂可作为一种原位凝胶化的眼部剂型。
