July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Thermo-responsive injectable microgel is able to achieve controlled drug release in the vitreous environment
Author Affiliations & Notes
  • Siyin Liu
    Department of Eye and Vision Science, University of Liverpool, Liverpool, Merseyside, United Kingdom
    College of Life Science, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Thomas McDonald
    Department of Chemistry, University of Liverpool, Liverpool, United Kingdom
  • Rob Van 'T Hof
    Department of Musculoskeletal Biology, University of Liverpool, Liverpool, United Kingdom
  • Victoria Kearns
    Department of Eye and Vision Science, University of Liverpool, Liverpool, Merseyside, United Kingdom
  • Footnotes
    Commercial Relationships   Siyin Liu, None; Thomas McDonald, None; Rob Van 'T Hof, None; Victoria Kearns, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3362. doi:
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    • Get Citation

      Siyin Liu, Thomas McDonald, Rob Van 'T Hof, Victoria Kearns; Thermo-responsive injectable microgel is able to achieve controlled drug release in the vitreous environment. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3362.

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

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Abstract

Purpose : Intravitreal injection leads to an initial burst release of drug and an extended period of underdosing below the therapeutic level. Thermo-induced microgel, poly(N-isopropyl acrylamide) (PNIPAm), was previously shown to achieve controlled release of encapsulated drugs in agarose tissue mimic. Herein, we describe the drug releasing behaviour of PNIPAm in an experimental porcine vitreous model by using micro-computed tomography (MicroCT).

Methods : PNIPAm microgels were prepared from NIPAm monomer and allylamine co-monomer by precipitation polymerisation under nitrogen atmosphere. Radiographic agent Optiray was used as intravitreal drug mimic (10%) and incorporated into PNIPAm suspension by vortexing. Vitreous humorous harvested from porcine eyes were placed in a 2ml modified syringe and pre-warmed to 37°C to mimic intraocular conditions. Optiray-containing PNIPAm microgels were injected into the vitreous models (n=2). Diffusion of Optiray was tracked by MicroCT scanning at serial time points over 15 hours, with 30 minutes’ interval between each scan. 10% agarose containing Optiray was used as controls (n=2). Signal intensity of Optiray in the microgel and the top position of the model were compared. The time required for 50% of Optiray to be released was also calculated. One-way ANOVA was used for statistical analysis.

Results : PNIPAm microgel rapidly aggregated to form a drug depot in pre-warmed porcine vitreous humorous. After 15.2 hours, Optiray concentration in PNIPAm depot remained significantly higher than other positions of the vitreous model (p<0.05), whereas its concentration in 10% agarose controls reached equilibrium throughout the model with no significant difference within 2.2 hours (p>0.30). The predicted time, extrapolated from the release curve, for 50% of Optiray to be released from 1% agarose was 3 hours whiles from PNIPAm was 55 hours.

Conclusions : Our results showed that PNIPAm microgels could be used to construct an injectable drug depot in the vitreous environment and provide long-term sustained release of drugs. This study has also demonstrated the potential of using MicroCT for non-invasive analysis of intraocular drug-release. Further in vivo studies will be needed to account for aqueous flow, drug absorption and saccadic movement.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

PNIPAm injected into the pre-warm vitreous model

PNIPAm injected into the pre-warm vitreous model

 

A. Diffusion of Optiray from PNIPAm: CT sagittal view
B. Signal intensity histogram

A. Diffusion of Optiray from PNIPAm: CT sagittal view
B. Signal intensity histogram

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