PolySciTech Thermogelling PLGA-PEG-PLGA used in development of cataract therapy to prevent blindness
Cataract
surgery is typically successful in returning sight to people who have suffered
from loss of sight due to cloudiness of the eye’s lense. One complication from
the surgery, however, is the formation of Posterior capsule opacity, which once
again removes vision by making it impossible to see through the affected
portions of the eye. Recently, researchers at The Ohio State University
utilized PLGA-PEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AK024) to develop a
thermogel-based delivery system for cyclosporine A to prevent PCO. This
research holds promise to restore sight to people affected by this condition.
Read more: Gervais, Kristen J. "Evaluation of a biodegradable thermogel
polymer for intraocular delivery of cyclosporine A to prevent posterior capsule
opacification." PhD diss., The Ohio State University, 2017. (https://etd.ohiolink.edu/pg_10?0::NO:10:P10_ACCESSION_NUM:osu1492101014927609, https://etd.ohiolink.edu/!etd.send_file?accession=osu1492101014927609&disposition=inline)
“Abstract: Purpose:
To utilize a thermosensitive hydrogel (thermogel) polymer to achieve sustained
release of cyclosporine A (CsA) for targeted destruction of lens epithelial
cells (LEC) and reduction of posterior capsule opacification (PCO) after
cataract surgery. Part I of the study evaluated the drug delivery system in an
ex vivo canine model of PCO, while Part II evaluated intraocular delivery in an
in vivo rabbit model. Methods. A PLGA-PEG-PLGA thermogel polymer was formulated
to release CsA ([300µg/mL]) or vehicle (ethanol). PART I: Extracapsular
cataract extraction and intraocular lens (IOL) placement were performed in 24
canine cadaver globes. Lens capsule explants with residual LEC were treated
with 200µL of CsA-eluting (n=12) or vehicle-eluting (n=12) thermogel and
maintained in culture. Posterior capsule coverage by LEC was graded following 7
(n=8), 14 (n=6), or 28 (n=10) days of treatment. Following histology, LEC were
manually quantified via light microscopy from capsules treated for 28-days. CsA
concentration in culture media was quantified by tandem liquid
chromatography-mass spectrometry (LC-MS/MS) at each time point. Differences in
percent posterior capsule coverage and LEC counts were analyzed by the
student’s t-test with Welch’s correction. PART II: Phacoemulsification cataract
surgery and IOL placement were performed in 10 adult rabbits (20 eyes). Ten left
eyes served as negative controls and were treated with viscoelastic material
only. Five right eyes were treated with 200µL CsA-eluting thermogel polymer,
and five right eyes were treated with vehicle-eluting thermogel polymer.
Clinical ophthalmic examination parameters and PCO grading were performed daily
for 6 days post-operatively, and then weekly until the termination of the study
at 49 days. Aqueous humor samples were analyzed for CsA concentration at day 6
post-operatively. Following euthanasia, globes were collected and analyzed
histologically for degree of PCO formation and any evidence of ocular toxicity.
Clinical examination parameters were compared between treatment groups using
the Wilcoxon signed rank or Wilcoxon rank sum test. Results. PART I: Posterior
capsule coverage by LEC was significantly reduced in CsA-thermogel treated
capsules compared to vehicle-treated capsules. Histologic LEC counts were
significantly lower in CsA-thermogel treated capsules. Cumulative CsA release
from the thermogel was greater than 10µg/mL over a minimum of 7 days. PART II:
No significant differences in clinical PCO scores were identified when
comparing treatment with CsA-eluting thermogel to vehicle-eluting thermogel.
The rate of onset and severity of PCO formation were significantly decreased in
thermogel-treated eyes (CsA- and thermogel-treated data combined) compared to
non-thermogel-treated eyes up to 4 weeks post-operatively. At the conclusion of
the study, no significant differences in PCO formation were found clinically or
histologically between treatment groups. The mean aqueous humor CsA level at
day 6 post-operatively was 3.2pg/mL. No direct toxic effects of the thermogel
polymer or CsA were documented in any eyes. Conclusions. Use of a CsA-eluting
thermogel polymer may be a viable pharmacologic method for inducing targeted
LEC death and reducing PCO formation. Intraocular administration of the drug
delivery system is feasible and does not result in ocular toxicity.”
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