June 2020
Volume 61, Issue 7
ARVO Annual Meeting Abstract  |   June 2020
Phenylboronic Acid Based Mucoadhesive Polymeric Micelles for Reduction in Intra-Ocular Pressure (IOP) during Glaucoma
Author Affiliations & Notes
  • Aftab Taiyab
    Chemical Engineering, McMaster University, Milton, Ontario, Canada
  • Jennifer Tian
    McMaster University, Ontario, Canada
  • Lina Liu
    McMaster University, Ontario, Canada
  • Frances Lasowski
    McMaster University, Ontario, Canada
  • Ben B Muirhead
    McMaster University, Ontario, Canada
  • Talena Rambarran
    McMaster University, Ontario, Canada
  • Monica Akula
    Chemical Engineering, McMaster University, Milton, Ontario, Canada
  • Paula Deschamps
    Chemical Engineering, McMaster University, Milton, Ontario, Canada
  • Terete Borras
    University of North Carolina at Chapel Hill, North Carolina, United States
  • Trevor Williams
    University of Colorado , Colorado, United States
  • Judith A West-Mays
    Chemical Engineering, McMaster University, Milton, Ontario, Canada
  • Heather Sheardown
    McMaster University, Ontario, Canada
  • Footnotes
    Commercial Relationships   Aftab Taiyab, None; Jennifer Tian, None; Lina Liu, None; Frances Lasowski, None; Ben Muirhead, None; Talena Rambarran, None; Monica Akula, None; Paula Deschamps, None; Terete Borras, None; Trevor Williams, None; Judith West-Mays, None; Heather Sheardown, None
  • Footnotes
    Support  Ontario Research Fund (C20/20: Responsive Materials for Ocular Therapy)
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1359. doi:
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      Aftab Taiyab, Jennifer Tian, Lina Liu, Frances Lasowski, Ben B Muirhead, Talena Rambarran, Monica Akula, Paula Deschamps, Terete Borras, Trevor Williams, Judith A West-Mays, Heather Sheardown; Phenylboronic Acid Based Mucoadhesive Polymeric Micelles for Reduction in Intra-Ocular Pressure (IOP) during Glaucoma. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1359.

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

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Purpose : Conventional anterior drug delivery methods are ineffective due to the low bioavailability caused by static and dynamic barriers which result in rapid drug clearance. Due to the longer clearance time of mucins compared with tears, we hypothesize that Phenylboronic Acid (PBA), a known mucoadhesive; based micelles can enhance drug delivery to the anterior eye. PBA based micelles can increase retention time, bioavailability, and can be used can be used for drug repurposing and delivering anti-glaucoma drug in a more efficient manner.

Methods : Poly (Llactide) bpoly (methacrylic acid-co-3-acrylamidophenylboronic acid) block copolymer micelles previously developed in the Sheardown lab were synthesized by free radical polymerization. Nuclear magnetic resonance (NMR) was used to confirm structure and molecular weight. Drug release studies was performed using micelle-Latanoprost (LTNP) formulation in dialysis tubing released into simulated tear fluid. Drug was detected via high performance liquid chromatography (HPLC). A conditional knock-out (KO) mouse model with increased IOP made by deleting Tfap2b specifically in angle tissues following MgpCre recombination was used to study the effect of micelle-latanoprost formulation. The eyes of the conditional KO mouse and its wild-type littermates were treated with vehicle, latanoprost or micelle-latanoprost formulation. IOP pressure measurements were acquired using the TonoLab rebound tonometer.

Results : NMR showed similarities between the micelles tested and those previously synthesized in terms of structure and molecular weight. The drug release profile follows pseudo zero order kinetics up until day 12, where 80% drug has been released and the remaining drug is cleared with the micelles. The study on entrapment efficiencies shows an entrapment efficiency of 23.7 ± 1.2%. A significant increase (~2-fold) in IOP was observed in mutants when compared with controls at both P30 (n=6; p<0.0001) and P40 (n=10; p<0.0001). A sustained decrease in IOP in KO mice treated with micelle- latanoprost formulation was observed compared to ones treated with latanoprost alone.

Conclusions : Anterior drug delivery methods for lowering IOP, and thus reducing the progression of glaucoma, can be improved by using PBA based micelles due to their ability to produce a sustained release as well as improve bioavailability through increased drug residence time.

This is a 2020 ARVO Annual Meeting abstract.


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