June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
In vivo comparison of intracameral and intravitreal implantation of Miniaturized Injectable Delivery System (MIDS) for timolol maleate
Author Affiliations & Notes
  • Chu Jian Ma
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Youning Zhang
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • John Dickson
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Daniel Bernards
    Bioengineering, University of California San Francisco, San Francisco, California, United States
  • Murty Vyakarnam
    Oculinea, California, United States
  • Tejal Desai
    Bioengineering, University of California San Francisco, San Francisco, California, United States
  • Robert Bhisitkul
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Chu Jian Ma None; Youning Zhang None; John Dickson None; Daniel Bernards Oculinea, Code I (Personal Financial Interest); Murty Vyakarnam Oculinea, Code I (Personal Financial Interest); Tejal Desai Oculinea, Code I (Personal Financial Interest); Robert Bhisitkul Oculinea, Code I (Personal Financial Interest)
  • Footnotes
    Support  NH Grant 5R01EY021574; Edward N and Della L Thome Memorial Foundation P0533367; That Man May See AW070823
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4158 – F0150. doi:
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    • Get Citation

      Chu Jian Ma, Youning Zhang, John Dickson, Daniel Bernards, Murty Vyakarnam, Tejal Desai, Robert Bhisitkul; In vivo comparison of intracameral and intravitreal implantation of Miniaturized Injectable Delivery System (MIDS) for timolol maleate. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4158 – F0150.

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

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Abstract

Purpose : There is an unmet need for sustained drug delivery for glaucoma pharmacotherapy. We describe a miniaturized injectable delivery system (MIDS) based on biodegradable polymers engineered for zero-order release of timolol maleate for a minimum of 8 weeks, injected into the intracameral (IC) or intravitreal (IV) space

Methods : MIDS device is a cylindrical implant (unique thin-film semi-permeable polymeric membrane encapsulating a pharmaceutical core) that provides zero-order drug delivery, and fabricated for use with a 23-gauge needle. In vitro pharmacokinetics studies were performed in temperature- and pH-controlled fluid chambers over 20 weeks. MIDS devices were injected into the IC and IV space of New Zealand rabbits. Eyes were examined weekly, with intraocular pressures (IOP) measurements (Tono-Vet, iCare). At sacrifice at 8 weeks post-injection, eyes were enucleated and dissected, and ocular compartment drug concentrations were determined by lipid chromatography-tandem mass spectrometry. Two tailed student’s t-test was used for statistical analysis.

Results : In vitro studies of MIDS devices demonstrated approximate zero-order drug release over 1 to 5 months. Ocular safety was acceptable, without significant intraocular inflammation. At 8-week post injection, in vivo studies demonstrated that IOP in experimental eyes was lowered by 11.1±6.5% (N = 5, p = 0.019) for IC devices and 14.6±3.9% (N = 5, p = 0.020) for IV devices. Analysis of ocular tissues revealed different concentration profiles for IC vs. IV at 8 weeks (in ng/g; except for aqueous in ng/mL): aqueous 28.45±5.44 vs 4.50±2.15, iris 36.67±9.73 vs 32.52±25.30, vitreous 0.28±0.26 vs 37.17±19.03, and ciliary body 14.39±3.59 vs 50.93±18.64. Blood concentration of drug was below the quantitation limit (< 0.4ng/ml) at 8 weeks for both groups

Conclusions : MIDS devices achieved zero-order release of timolol maleate in vitro. Over 8 weeks, implanted eyes' mean IOPs were lowered compared to controls at each weekly timepoint with similar levels of reduction between IC and IV. Target tissue drug concentrations at the ciliary body at 8 weeks exceeded therapeutic levels. Compared to IC, IV injection appeared to result in 4-5 times higher drug levels in the ciliary body. The technology has the potential to be provide continuous IOP-lowering therapy to overcome issues of patient compliance with daily eye drops

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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