July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
An Injectable Collagen Depot for Subconjunctival Drug delivery
Author Affiliations & Notes
  • Saja Muwaffak
    Pharmaceutics, The School of Pharmacy, University College London, London, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
  • Peng Tee Khaw
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
  • Richard A Eiferman
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Steve Brocchini
    Pharmaceutics, The School of Pharmacy, University College London, London, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
  • Dale P DeVore
    Sanova Biosciences Inc, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Saja Muwaffak, None; Peng Khaw, None; Richard Eiferman, None; Steve Brocchini, None; Dale DeVore, None
  • Footnotes
    Support  EPSRC Grant EP/L01646X
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3354. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Saja Muwaffak, Peng Tee Khaw, Richard A Eiferman, Steve Brocchini, Dale P DeVore; An Injectable Collagen Depot for Subconjunctival Drug delivery. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3354.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Long acting injectable formulations of anti-scarring agents are needed to treat subconjunctival fibrosis. An in-situ polymerisable collagen (IPC) is being developed as an injectable depot for subconjunctival drug delivery. Pirfenidone (water soluble) and illomastat (poorly water soluble) were evaluated to determine their effects on collagen gelling and drug release profiles.

Methods : The IPC was prepared by gradually increasing the pH of collagen to pH 7 in the presence of ethylenediaminetetraacetic acid. The formulations were then prepared using both drugs and the drug release was then carried out at 37 °C within a flow model (2 µL/min) for 14 days.

Dynamic mechanical analysis was conducted to characterise the mechanical stiffness of the gel formulations. The effect of freeze drying on the gel properties in formulation was investigated.

Results : Gelling was characterised by fibril formation which began within a few seconds after contact of the IPC solution with biologically relevant media (e.g. PBS) at 37 °C.

As seen in Figure 1, the ilomastat formulation showed a slow-release profile (at 10 mg/mL) where the drug release occurred over 14 days. The more water soluble pirfenidone formulation released all the drug in 3 days. In the case of ilomastat, the formation of a micro-precipitate (less than 100 µm) and precipitate entrapment inside the gel may have caused the slower dissolution process.

The mechanical stiffness of the IPC gel before drug loading was approximately 1.2 kPa which was reduced by 25% after the formulation process. Furthermore, there was no significant difference in the mechanical stiffness of the formulation after extrusion with a 30G needle, compared to prior to extrusion. Furthermore, the time for gelling and the gelling properties were not affected by freeze drying.

Conclusions : IPC has the potential to deliver poorly-soluble drugs such as illomastat due to their precipitation inside the gel. Therefore, the IPC can be a useful vehicle for powdered formulations of drugs. Drug precipitation within the IPC results in a slow-release drug profile which could be beneficial for conditions such as subconjunctival fibrosis.

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

 

Figure 1. The dissolution profile of the ilomastat and pirfenidone formulation.

Figure 1. The dissolution profile of the ilomastat and pirfenidone formulation.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×