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    Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

    Year: 2012

    Journal: PHARMACEUTICAL RESEARCH Volume 29, Number 8 (2012), 2329-2340, DOI: 10.1007/s11095-012-0761-1, 20120922

    Authors: I. Bravo-Osuna(1), M. Noiray(2), E. Briand(2), A. M. Woodward(3), P. Argüeso(3), I. T. Molina Martínez(1), R. Herrero-Vanrell(1), G. Ponchel(2)

    Last authors: G. Ponchel

    Organizations: 1. Dept. of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid (UCM), Madrid, Spain 2. CNRS UMR 8612, Université de Paris Sud Laboratoire de Physicochimie, Pharmacotechnie & Biopharmacie, Chatenay-Malabry, France 2. Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute, Boston, Massachusetts 02114, USA ibravo@farm.ucm.es

    Country: Spain, France, USA, US, United States, United States of America, America

    Purpose  

    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.

    Methods  

    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).

    Results  

    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-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)>> CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %).

    Conclusions  

    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.