June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Ocular injection characteristics and in vitro release profiles of lipophilic dye using thermogel PLGA-PE-PLGA as a sustained-release drug delivery device
Author Affiliations & Notes
  • Eva Abarca
    North Carolina State University, Raleigh, NC
  • Page Potter
    North Carolina State University, Raleigh, NC
  • Jacklyn Salmon
    North Carolina State University, Raleigh, NC
  • Brian Gilger
    North Carolina State University, Raleigh, NC
  • Footnotes
    Commercial Relationships Eva Abarca, Clearside (F); Page Potter, None; Jacklyn Salmon, Clearside (F); Brian Gilger, Clearside (F), Allergan (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5052. doi:
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      Eva Abarca, Page Potter, Jacklyn Salmon, Brian Gilger; Ocular injection characteristics and in vitro release profiles of lipophilic dye using thermogel PLGA-PE-PLGA as a sustained-release drug delivery device. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5052.

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

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Purpose: Thermosensitive biodegradable gels may be useful for sustained delivery of drugs intravitreally (IVT) or into the suprachoroidal space (SCS). The purpose of this study is to determine if a thermogel polymer can improve release kinetics of lipophilic carbocyanine dye (DiI) and to evaluate if these polymers can be effectively injected into the eye.

Methods: Release kinetics of DiI from poly-(d,l-lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG-PLGA) was determined in vitro. Liquid 20% PLGA-PEG-PLGA (200 µl at 2°C) was added to glass vials, either alone or mixed with 0.1 mg DiI crystals, 0.1 mg DiI dissolved in ethanol, or 0.1 mg DiI dissolved in ethanol with 2% hyaluronic acid (HA). A 5th group had no PLGA-PEG-PLGA, just 0.1 mg DiI crystals. The vials were then maintained at 37°C allowing gels to form,1 ml of PBS was added and daily samples were collected for analysis by spectrofluoroscopy for 21 days. To characterize ocular injection and gel formation, 12 normothermic ex-vivo pig eyes were injected with liquid thermogel (2°C) with 0.1 mg DiI. Six eyes were injected into the SCS using a 33 gauge 750 depth microneedle, whereas 6 eyes were injected IVT. High-frequency (50Mhz) or 20 Mhz ultrasound was used to image and to evaluate the effect and distension in the SCS or vitreous, respectively.

Results: Release of DiI from thermogel was significantly higher than DiI crystals over the first 7 days. Area under the curve (AUC) was significantly higher (P<0.001) in PLGA-PEG-PLGA-HA gels compared to the other gels, and the PLGA-PEG-PLGA-HA had highest Cmax at day one (Tmax) showing an initial burst release. Following SCS injection, a well demarcated hypoechoic structure formed in the anterior SCS (1.9 +/- 0.4 mm by 7.1 +/-1.3 mm). After IVT injection, a hyperechoic nearly spherical structure formed (3.9 +/- 0.8 mm by 5.3 +/-1.08 mm). Macroscopic exam of the sectioned eye showed a well delimited gel-like structure in the SCS and IVT in each eye.

Conclusions: PLGA-PE-PLGA thermogel resulted in sustained DiI release for 7 days. The more hydrophilic PLGA-PG-PLGA with HA exhibited a higher and more rapid release. SCS injections of liquid (2°C) PLGA-PE-PLGA are feasible using microneedles resulting in a well-defined gel in the SCS and IVT. The thermosensitive show promise as a sustained delivery system targeting the choroid and retina.

Keywords: 503 drug toxicity/drug effects • 452 choroid • 551 imaging/image analysis: non-clinical  

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