June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Biodegradable and Injectable Thermosensitive Pentablock Copolymers Hydrogels for Sustained Delivery of Proteins for Posterior Segment Ocular Diseases
Author Affiliations & Notes
  • Ashim K Mitra
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO
  • Sulabh Patel
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO
    Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
  • Ravi Vaishya
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO
  • Vibhuti Agrahari
    School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO
  • Footnotes
    Commercial Relationships Ashim Mitra, None; Sulabh Patel, None; Ravi Vaishya, None; Vibhuti Agrahari, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4141. doi:https://doi.org/
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      Ashim K Mitra, Sulabh Patel, Ravi Vaishya, Vibhuti Agrahari; Biodegradable and Injectable Thermosensitive Pentablock Copolymers Hydrogels for Sustained Delivery of Proteins for Posterior Segment Ocular Diseases. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4141. doi: https://doi.org/.

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

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Abstract

Purpose: To investigate the sustained delivery of protein therapeutics from biodegradable and injectable thermosensitive hydrogels for the treatment of ocular posterior segment diseases including age-related macular degeneration, macular edema and proliferative diabetic retinopathy. The hydrogel matrix protects protein therapeutics from enzymatic degradation and provides sustained release over a longer period of time, eliminating the need for monthly injections.

Methods: This study includes synthesis and characterization of triblock (TB) and pentablock (PBC) copolymers with an emphasis on effect of block arrangements of polymers, rheological properties, sol-gel transition, in vitro cytotoxicity/biocompatibility, in vitro release, release kinetics and in vitro degradation study. Purity and molecular weight were analyzed by NMR. Mw, Mn and PDI indices were examined by GPC. Crystallinity of TB and PBC were analyzed by XRD. Rheological properties were estimated with an Ubbelohde capillary viscometer. In vitro cell viability and biocompatibility studies were performed on ARPE 19 and RAW 264.7. In vitro release studies of proteins were performed in PBS, pH 7.4 at 340C. The release data was fitted to various kinetic models to investigate release mechanism. In vitro degradation studies were performed at four different incubation conditions, further subjected to GPC, XRD and ESM.

Results: NMR, GPC, FTIR and XRD analyses of TB and PBC provided complete characterization of the polymers. Results from sol-gel transition studies demonstrated that aqueous solutions of TB and PBC can immediately transform to hydrogel at 32-34 °C. PBC provide significantly longer sustained release of IgG relative to TB copolymers. Kinematic viscosity of aqueous solution of PBCs was noticeably lower than the TB copolymers suggesting easy syringeability. In Vitro biocompatibility and cell viability assay exhibited negligible release of cytokines. Based on the R2 value, best fit model was identified. Rapid degradation of TB and PBC depends on the amorphous and hydrophilic nature of thermosensitive polymer.

Conclusions: TB and PBC were evaluated for their utility as injectable hydrogel forming depot for sustained ocular protein delivery. These outcomes clearly suggest that PBC based controlled drug delivery system may serve as a promising platform for back of the eye complications.

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