title: Interfacial interaction between transmembrane ocular mucins and adhesive polymers and dendrimers analyzed by surface plasmon resonance.
abstract: OBJECTIVE
  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-NH(2)(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.
authors.affiliation: Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid (UCM), Madrid, Spain. ibravo@farm.ucm.es
authors.forename: I
authors.initials: I
authors.lastname: Bravo-Osuna
authors.forename: M
authors.initials: M
authors.lastname: Noiray
authors.forename: E
authors.initials: E
authors.lastname: Briand
authors.forename: A M
authors.initials: AM
authors.lastname: Woodward
authors.forename: P
authors.initials: P
authors.lastname: Argüeso
authors.forename: I T
authors.initials: IT
authors.lastname: Molina Martínez
authors.forename: R
authors.initials: R
authors.lastname: Herrero-Vanrell
authors.forename: G
authors.initials: G
authors.lastname: Ponchel
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000378:metabolism*; D002460:Cell Line; D048271:Chitosan / Q000378:metabolism*; D003315:Cornea / Q000166:cytology / Q000378:metabolism; D050091:Dendrimers / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000378:metabolism; D009077:Mucins / Q000302:isolation & purification / Q000378:metabolism*; D009883:Ophthalmic Solutions / Q000378:metabolism*; D056951:Photoelectron Spectroscopy; D058525:Quartz Crystal Microbalance Techniques; D020349:Surface Plasmon Resonance / Q000379:methods
chemical_list: D050091:Dendrimers; D009077:Mucins; D009883:Ophthalmic Solutions; C104700:PAMAM Starburst; D065347:Hypromellose Derivatives; D006820:Hyaluronic Acid; D008747:Methylcellulose; D048271:Chitosan; D002266:Carboxymethylcellulose Sodium