May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Transscleral Delivery of Nanoparticle Triamcinolone
Author Affiliations & Notes
  • S. Lee
    Ophthalmology, Emory University Eye Center, Atlanta, Georgia
    Ophthalmology, Soonchunhyang University Hospital, Seoul, Republic of Korea
  • C. Durairaj
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska
  • A. M. Laties
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania
  • R. S. Kadam
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska
  • Y. Mo
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska
  • D. H. Geroski
    Ophthalmology, Emory University Eye Center, Atlanta, Georgia
  • U. B. Kompella
    Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska
  • A. M. McGlinn
    Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania
  • H. F. Edelhauser
    Ophthalmology, Emory University Eye Center, Atlanta, Georgia
  • Footnotes
    Commercial Relationships  S. Lee, None; C. Durairaj, None; A.M. Laties, None; R.S. Kadam, None; Y. Mo, None; D.H. Geroski, None; U.B. Kompella, None; A.M. McGlinn, None; H.F. Edelhauser, None.
  • Footnotes
    Support  NEI grant P30-EY06360 and R24-EY01745 and by RPB
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4794. doi:https://doi.org/
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    • Get Citation

      S. Lee, C. Durairaj, A. M. Laties, R. S. Kadam, Y. Mo, D. H. Geroski, U. B. Kompella, A. M. McGlinn, H. F. Edelhauser; Transscleral Delivery of Nanoparticle Triamcinolone. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4794. doi: https://doi.org/.

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

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Abstract
 
Purpose:
 

To determine the ex vivo and in vivo transscleral permeability of nanoparticle triamcinolone (NTA) compared with commercially available triamcinolone acetonide (TA).

 
Methods:
 

The ex vivo permeability of NTA and TA (1.5 mg/ml) across human donor sclera was tested using a Lucite block perfusion chamber. Levels of NTA diffusing across the sclera were measured every 2 hours for 24 hours using HPLC. Pigmented rabbits (2.2 Kg) were given a subtenon injection in vivo in both eyes with NTA (1.0 mg/ 0.2 ml) or TA (20 mg/0.2 ml). One group (n = 20) of rabbits were euthanized at 2, 4, 6 hours post injection, enucleated, frozen, and dissected into different tissues. The second group of rabbits (n = 20) were euthanized at 2, 4, 6 hours post injection, enucleated, frozen, desiccated, and dissected into different tissues. Each group had a control (n = 4) and immediate euthanasia subgroups (IE) (n = 4) which were enucleated at 6 hours post injection. Drug concentration in the dissected tissues was measured using HPLC.

 
Results:
 

Ex vivo NTA had a faster transscleral permeability constant (Kconst) of 1.09 ± 0.42 x 10-5 cm/s compared to TA at 5.93 ± 2.90 x 10-9 cm/s. After 6 hours, retina/choroid level of TA was 3.78 ± 2.31 ng/mg and 1.91 ± 0.59 ng/mg with NTA. Vitreous level was 0.24 ± 0.22 ng/ml with TA and 9.73 ± 5.14 ng/ml with NTA after 6 hours. In dessicated eyes, TA concentration in the retina was 1.94 ± 0.65 ng/ml without immediate euthanasia (IE) and 34.89 ± 6.68 ng/mg with IE. TA concentration in the choroid was 12.71 ± 5.59 ng/mg without IE and 26.98 ± 4.44 ng/mg with IE at 6 hours.

 
Conclusions:
 

Both TA and NTA are able to diffuse across human and rabbit sclera. The retina/choroid concentration is comparable in both TA and NTA, however, NTA showed higher vitreous concentration with a small dose. Based on the dry desiccated tissue data, the choroid is a major barrier in transscleral drug delivery of TA and NTA.  

 
Keywords: drug toxicity/drug effects • retina • vitreous 
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