July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Ocular Pharmacokinetics of Insulin-loaded Thermoresponsive Biodegradable Nanogels
Author Affiliations & Notes
  • Tao L Lowe
    Pharmaceutical Sciences, Univ of Tennessee Health Science Ctr, Memphis, Tennessee, United States
  • Ftisum Sahle
    Pharmaceutical Sciences, Univ of Tennessee Health Science Ctr, Memphis, Tennessee, United States
  • Cameron Fili
    Comparative Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Darren Will
    Pharmaceutical Sciences, Univ of Tennessee Health Science Ctr, Memphis, Tennessee, United States
  • Steven Davison
    Comparative Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • David Hamilton
    Comparative Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Tao Lowe, None; Ftisum Sahle, None; Cameron Fili, None; Darren Will, None; Steven Davison, None; David Hamilton, None
  • Footnotes
    Support  NIH R01EY023853
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6003. doi:
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    • Get Citation

      Tao L Lowe, Ftisum Sahle, Cameron Fili, Darren Will, Steven Davison, David Hamilton; Ocular Pharmacokinetics of Insulin-loaded Thermoresponsive Biodegradable Nanogels. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6003.

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

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Abstract

Purpose : Diabetic retinopathy (DR) affects about one third of the estimated 285 million people with diabetes mellitus and is a leading cause of vision-loss worldwide. It is associated with retinal neurovascular degeneration and studies indicated that systemic, subconjunctival or intravitreal injection of insulin may reduce the risk of DR onset and progression. However, insulin has a short half-life and the risk of hypoglycemia limits patients’ ability to take enough insulin systemically. The purpose of this project is to develop thermoresponsive and biodegradable nanogels for aqueous loading and sustained release of intact insulin, and evaluate ocular pharmacokinetics of the insulin-loaded nanogels after subconjunctival injection. Successful completion of the project will have significant impact on effective therapies for the prevention and treatment of DR.

Methods : Insulin loaded, thermoresponsive, biodegradable nanogels, containing N-isopropylacrylamide, Dex-lactate-HEMA and acrylic acid were synthesized by surfactant free emulsion polymerization. The nanoparticles are being characterized with respect to size, zeta potential, yield, and insulin loading efficiency and capacity. The in vitro release kinetics study of insulin from the nanogels is being carried out using dialysis method over one month period of time. The released insulin is quantified using a developed UPLC method. Insulin-loaded and fluorescent dye 5-DTAF-labeled nanogels were subconjunctivally injected in the right eyes of SD rats (5/group) at 20 mg/mL. The ocular pharmacokinetics of the nanogels and insulin released from the nanogels in the ocular tissues post 1 and 7 day injection are studied by using fluorescent reader and LC-MS/MS, respectively.

Results : Negatively charged, 100 – 200 nm, insulin-loaded, thermoresponsive, and biodegradable nanogels with insulin loading efficiency of > 98% and yield > 68% were obtained. An efficient tissue homogenization method was developed for the nanogels and insulin. The nanogels can sustain release insulin in vitro and to the retina after intravitreal and subconjunctival injections in SD rats.

Conclusions : Thermoresponsive, biodegradable nanogels that enhance the scleral and BRB permeability and sustain the release of insulin were developed. The insulin-loaded nanogels show promise for the treatments of diabetic retinopathy in the future.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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