March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Prolongation of Proparacaine Corneal Anesthesia by an In Situ Cross Linked Hydrogel of Carboxymethylcellulose
Author Affiliations & Notes
  • Houman D. Hemmati
    Ophthalmology, Mass. Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts
    Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
  • Miguel Manzano-Garcia
    Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
  • Daniel S. Kohane
    Anesthesiology, Laboratory for Biomaterials and Drug Delivery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts
  • Robert Langer
    Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
  • Footnotes
    Commercial Relationships  Houman D. Hemmati, In-situ crosslinked CMC Hydrogels (P); Miguel Manzano-Garcia, None; Daniel S. Kohane, In situ-crosslinked CMC Hydrogels (P); Robert Langer, In situ-crosslinked CMC Hydrogels (P)
  • Footnotes
    Support  Boston Keratoprosthesis Funds
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 499. doi:
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      Houman D. Hemmati, Miguel Manzano-Garcia, Daniel S. Kohane, Robert Langer; Prolongation of Proparacaine Corneal Anesthesia by an In Situ Cross Linked Hydrogel of Carboxymethylcellulose. Invest. Ophthalmol. Vis. Sci. 2012;53(14):499.

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

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Abstract
 
Purpose:
 

To formulate and characterize a rapid hydrogel-forming eye drop delivery excipient designed to provided extended release of a topical anesthetic drug to the ocular surface.

 
Methods:
 

Periodate oxidation of carboxymethylcellulose (CMC) was performed to generate aldehyde-modified CMC (CMC-ALD). Modification of CMC with adipic dihydrazide (ADH) was performed to generate ADH-modified CMC (CMC-ADH). Separate 0.5% proparacaine solutions were created in phosphate-buffered saline (PBS) with CMC-ALD, CMC-ADH, unmodified CMC, and without CMC. 1:1 mixtures of CMC-ALD and CMC-ADH solutions were created to test hydrogel formation time, adhesiveness, and optical clarity. 25 uL of each of the aforementioned solutions were applied to the corneas of adult male Sprague Dawley rats, with one group of animals receiving 25 uL of PBS alone as a negative control (n=6 rats per group). Hydrogel eyes received 12.5 uL each of CMC-ALD and CMC-ADH simultaneously. Corneal sensation was measured by Cochet-Bonnet esthesiometry 1-2 times a day for 10 days.

 
Results:
 

CMC immediately cross-linked through hydrazone bonds (Figure 1) to form optically clear, pliable hydrogels on both glass slides and rat eyes. In situ cross-linked CMC hydrogel prolonged the duration of topical anesthesia by at least 9 days, significantly longer than unmodified CMC (p<0.05).

 
Conclusions:
 

In situ cross-linked hydrogels of CMC can potentially be used to dramatically prolong the duration of topically-delivered ophthalmic drugs.  

 

 
Keywords: cornea: tears/tear film/dry eye • wound healing • drug toxicity/drug effects 
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