April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Shear-thinning, associative, and mucoadhesive hydrogels for improved eyedrop formulations
Author Affiliations & Notes
  • sahar mokhtari
    Chemical Engineering, Mcmaster, Hamilton, ON, Canada
  • Paniz Sheikholeslami
    Chemical Engineering, Mcmaster, Hamilton, ON, Canada
  • Niels Smeets
    Chemical Engineering, Mcmaster, Hamilton, ON, Canada
  • Todd Hoare
    Chemical Engineering, Mcmaster, Hamilton, ON, Canada
  • Footnotes
    Commercial Relationships sahar mokhtari, None; Paniz Sheikholeslami, None; Niels Smeets, None; Todd Hoare, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 461. doi:
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      sahar mokhtari, Paniz Sheikholeslami, Niels Smeets, Todd Hoare; Shear-thinning, associative, and mucoadhesive hydrogels for improved eyedrop formulations. Invest. Ophthalmol. Vis. Sci. 2014;55(13):461.

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

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Abstract
 
Purpose
 

Most existing eyedrop formulations consist primarily of dilute solutions of water-soluble polymers. While these solutions provide temporary relief of dry eye or a means to transport a drug to the cornea, dilute solutions are quickly cleared from the eye via blinking, resulting in low drug uptake and the need for multiple treatments per day; in contrast, more viscous polymer solutions can cause discomfort or irritation of the ocular surface. Highly shear-thinning polymer solutions that can flow upon the application of shear but form gels at rest and(even more ideally)act to stabilize the tear film would instead be ideal for eyedrop formulations.

 
Methods
 

Amine-functionalized poly(N-vinylpyrrolidone) linear polymers are grafted with(1) C8-C16 hydrophobic chains (via condensation of alkyl halides) and(2)(optionally) mucoadhesive phenylboronic acid (PBA) groups (via reductive amination). The resulting polymers interact specifically with each layer of the tear film in addition to self-associating to form a hydrogel. Mixing this polymer solution with a cyclodextrin-grafted hyperbranched polymer (prepared by the Strathclyde methodology using dodecanethiol as a chain transfer agent to graft hydrophobes on chain ends in a single step) creates an associative hydrogel containing a functional nanodomain.

 
Results
 

Intermolecular association of neighboring hydrophobic grafts yields a three-dimensional polymer network that remains transparent even at high polymer fractions. The temporal rheology of the mixture as can be tuned based on the density of hydrophobes and the hyperbranched polymer content and architecture.Increasing the hyperbranched content in the mixture increases the magnitude of shear thinning and the speed of viscosity recovery following shear(Fig.1);we hypothesize that the compact globular structure of hyperbranched polymer promotes more facile interaction between hydrophobic groups and streaming of the polymers. Ocular compatibility testing indicated no adverse effects of the formulation at the front of the eye, while injection of the formulation into the vitreous induced no observable retinal toxicity or opacification in a rat model(Fig.2).

 
Conclusions
 

The transparency, shear thinning ability, and tunable functionality of the graft copolymers investigated suggest potential applications of these materials not only as(optionally medicated)eyedrops but also as potential vitreal replacements.

     
Keywords: 486 cornea: tears/tear film/dry eye • 485 cornea: surface mucins  
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