John Garner

PEG-PLA from PolySciTech used in development of ocular-delivery system to treat inflammation

Blog Post created by John Garner on Apr 13, 2018

2018 Ocular delivery.jpg

Inflammatory diseases are typified by an over-reaction of the human immune system against either some trigger or, in some-cases, without a specific trigger. Many diseases are caused by inflammation, however delivery of anti-inflammatory drugs is not always easily accomplished due to location or other disease complications. Recently, researchers at Stony Brook University and Medicon Pharmaceuticals utilized PEG-PLA (Polyvivo AK005) from PolyScitech (www.polyscitech.com) to generate anti-inflammatory nanoparticles for delivery of Phospho-sulindac to the ocular region. Read more: Robert A. Honkanen, Liqun Huang, Gang Xie, Basil Rigas “Phospho-sulindac is efficacious in an improved concanavalin a-based rabbit model of chronic dry eye disease” Translational Research (2018) https://www.sciencedirect.com/science/article/pii/S1931524418300562

 

“Abstract: Dry eye disease (DED), an inflammatory disease of the ocular surface, affects 15% of humans worldwide. No satisfactory treatment exists for DED partly due to the lack of informative animal models of this disease. We evaluated the anti-inflammatory phosphosulindac (PS) for the treatment of DED, using a new rabbit model of chronic DED. In this model, based on the Concanavalin A (Con A) acute DED model, we injected weekly x3 all lacrimal glands with ConA under ultrasound guidance, which prolonged DED to >3 weeks; and used concurrently four parameters of efficacy: tear break up time (TBUT), tear osmolarity, Schirmer's test, and tear lactoferrin levels, making efficacy assessment robust. Rabbits with DED (n=8-10 eyes/group) were treated topically with PS or vehicle 3x/day for 21 days. PS restored to normal TBUT, tear osmolarity and lactoferrin levels (p<0.0001–0.04) but did not significantly improve Schirmer's test. PS showed no side effects and was much more efficacious than cyclosporine or lifitegrast. PS suppressed the activation of NF-κB; the levels of TGF-β, IL-1β, IL-6 and IL-8; the levels MMP-1 and MMP-9 and MMP activity in the cornea. Levels of PGE2 in tears and cornea were preserved in PS-treated rabbits. Ketorolac and diclofenac, two ophthalmic NSAIDs that cause corneal melt, nearly completely suppressed PGE2 levels but had no effect on MMPs. PS's effects on PGE2 and MMPs likely account for its apparent ocular safety. Our results establish an animal model for DED suitable for drug efficacy studies and indicate that PS merits further evaluation for DED. List of abbreviations: PS, phosphosulindac; DED, dry eye disease; Con A, concanavalin A; TBUT, tear break up time; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TGF-β, transforming growth factor beta; IL-1β, interleukin 1 beta; IL-6, interleukin 6; IL-8, interleukin 8; MMP, matrix metalloproteinase; PGE2, progstaglandin E2; NSAIDs, nonsteroidal anti-inflammatory drugs; MAPKs, mitogen activated protein kinases; PEG-PLA, polyethylene glycol-block-polylactic acid; IU, international units; ml, milliliter; NZW, New Zealand White; RPM, revolutions per minute; RIPA, radio immunoprecipitation assay; SDS, sodium dodecyl sulphate; EMSA, electophoretic mobility shift assay; ILG, inferior lacrimal gland; PSLG, palpebral portion of superior lacrimal gland; OSLG, orbital portion of superior lacrimal gland; SLG, superior lacrimal gland; US, ultrasonography; BSA, bovine serum albumin; ELISA, enzyme-linked immunosorbent assay; H&E, hematoxylin and eosin; SEM, standard error of the mean; SD, standard deviation; PBS, phosphate buffered saline; TOsm, tear osmolarity; STT, Schirmer's tear test; JNK, c-Jun N-terminal kinases; ERK, extracellular signal regulated kinases; IC50, half maximal inhibitory concentration”

 

  BPCR conference

(August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Outcomes