April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Carboxilane Dendrimers For Ophthalmic Administration. Mucoadhesion studies
Author Affiliations & Notes
  • Irene Bravo-Osuna
    Pharmaceutical Technology, University Complutense of Madrid, Madrid, Spain
  • Noiray Magali
    CNRS UMR 8612, Université de Paris Sud, Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, Paris, France
  • Ashley Woodward
    Schepens Eye Research Institute, Dep. of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Pablo Argüeso
    Schepens Eye Research Institute, Dep. of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Rocio Herrero-Vanrell
    Pharmaceutical Technology, University Complutense of Madrid, Madrid, Spain
  • Irene Teresa Molina-Martinez
    Pharmaceutical Technology, University Complutense of Madrid, Madrid, Spain
  • Rafael Gómez
    Dep. of Inorganic Chemistry, School of Pharmacy, University of Alcalá (UAH), Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Alcalá de Henares, Spain
  • FJ de la Mata
    Dep. of Inorganic Chemistry, School of Pharmacy, University of Alcalá (UAH), Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Alcalá de Henares, Spain
  • Manuel Guzmán Navarro
    Dep. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Alcalá (UAH), Alcalá de Henares, Spain
  • Gilles Ponchel
    CNRS UMR 8612, Université de Paris Sud, Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, Paris, France
  • Footnotes
    Commercial Relationships  Irene Bravo-Osuna, None; Noiray Magali, None; Ashley Woodward, None; Pablo Argüeso, None; Rocio Herrero-Vanrell, None; Irene Teresa Molina-Martinez, None; Rafael Gómez, None; FJ de la Mata, None; Manuel Guzmán Navarro, None; Gilles Ponchel, None
  • Footnotes
    Support  Institute de Chimie du CNRS. Research Group UCM 920415 (GR58/08). NIH/NEI Grant No. R01EY014847 (PA).
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 424. doi:
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      Irene Bravo-Osuna, Noiray Magali, Ashley Woodward, Pablo Argüeso, Rocio Herrero-Vanrell, Irene Teresa Molina-Martinez, Rafael Gómez, FJ de la Mata, Manuel Guzmán Navarro, Gilles Ponchel; Carboxilane Dendrimers For Ophthalmic Administration. Mucoadhesion studies. Invest. Ophthalmol. Vis. Sci. 2011;52(14):424.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To evaluate the interaction between purified ocular surface mucins and carbosilane dendrimers-generation1, 2 & 3-, intended for drug delivery in ophthalmology, using Biosensor technology

Methods: : Ocular surface mucins were purified from stratified cultures of human corneal limbal epithelial (HCLE) cells using size-exclussion chromatogaphy followed by isopycnic density gradient centrifugation. Surface plasmon resonance (SPR) technique was chosen to evaluate the interaction of dendrimers with those ocular mucins. Saline solutions of carbosilane dendrimers (5-10 µM) were passed over the sensor chip, where mucins were previously immobilized, for 300s at 10 µl/min. Afterwards, the sensorgram was collected until equilibrium was reached. Studies were performed in triplicate at 35ºC.

Results: : As determined by western blot using the M11 antibody against MUC16, purified samples from HCLE cells consisted of mucin with a buoyant density range of 1.26 to 1.44 g/ml. Anionic dendrimers showed SPR sensorgrams indicative of non-molecular adhesion. A significant part of cationic dendrimers put in contact with mucins were retained in the mucin layer. The intensity of this interaction was statistically higher for G3 (18 NH2 surface groups), where 66 dendrimer molecules appeared associated to one mucin molecule, in comparison to the G2 (12 NH2) and G1 (6 NH2), where the dendrimer-mucin ratio was 27:1 and 29:1 respectively.

Conclusions: : Results demonstrate the deep interaction of carbosilane dendrimers with ocular mucins and support the utility of dendrimers as new drug delivery systems for topical ophthalmic drug administration.

Keywords: cornea: surface mucins 
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