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Brian C Gilger, Jacklyn H Salmon, Sulabh P Patel, Poonam Velagaleti, Sidney L Weiss, Ashim K Mitra, Ulrich Grau; Evaluation of ocular biocompatibility and duration of a bioerodible intravitreal pentablock co-polymer thermosensitive gel and/or nanoparticle ocular drug delivery system. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5998. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the ocular biocompatibility and duration in the vitreous of a novel bioerodible pentablock co-polymer (PBC) thermosensitive gel, PBC nanoparticles (NPs), or PBS nanoparticles suspended in PBC gel after intravitreal (IVT) administration.
100 uL of filter or gamma-sterilized PBC gel, PBC NPs, or PBC NPs in gel were injected IVT in normal New Zealand White (NZW) Rabbits. Clinical ocular inflammatory scores (OIS) and intraocular pressure (IOP) were measured daily for 7 days, then weekly through 20 weeks. Photopic electroretinography (ERG) (all rabbits) and ocular histopathology (group subsets) were performed at 0, 1, 4,and 16 weeks after injection.
PBC gel, NPs, or NPs in gel were injected into the central vitreous through a 27G needle without difficulty. The PBC gel (+/- NPs) created a solid gel depot at the site of injection, while the free NPs dispersed throughout the vitreous. Duration of PBC gel was 14 to 18 weeks and PBC NPs and NPs in gel duration was greater than 20 weeks. Mild elevated OIS were noted in all eyes for 2-3 days after injection and returned to baseline by 7 days and remained at baseline for 20 weeks, except for eyes with NPs only, which had mildly elevated scores at 1 week and again at 8 weeks days after injection. IOP and ERG values were not different than baseline at 1, 4,and 16 weeks after injection. Ocular histopathology revealed mild inflammatory infiltrate in eyes injected with NPs at 7 days after injection, however, eyes 1, 4, and 16 weeks after injection revealed no PBC gel-associated inflammation or toxicity.
Results from this study suggest that IVT PBC gel and PBC NPs in gel were well tolerated in NZW rabbits without signs of inflammation or toxicity except for inflammation associated with the injection procedure. Advantages of this novel drug delivery system include the ability to inject through a small needle, the containment of NPs within the gel, the long duration (4 months or longer) in the eye, and the excellent ocular biocompatibility. These advantages suggest that the bioerodible, thermosensitive PBC gel would be an ideal sustained drug delivery system for the ocular posterior segment and a major advancement for treatment of chronic ocular diseases such as age related macular degeneration.
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