Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

Chiang, Bryce; Kim, Yoo Chun; Edelhauser, Henry F.; Prausnitz, Mark R.

doi:10.1016/j.exer.2016.03.008

Cited by 40 publications

(38 citation statements)

References 24 publications

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“…These species differences may or may not alter SCS distribution. For example, as we showed previously (Chiang et al, 2016b), there are different anatomical barriers in rabbits versus humans that affect circumferential particle spread. Human clinical trials will be needed to investigate SCS distribution, as it applies to human health.…”

Section: Discussionsupporting

confidence: 53%

“…A linear fit to the data yielded a poor correlation (r 2 = 0.51 for particles and 0.67 for fluorescein), whereas an exponential fit was better (r 2 = 0.90 for particles and r 2 = 0.69 for fluorescein), which is consistent with the observation that area initially increases and appears to approach a plateau value slightly below 50% area coverage for particles and slightly above 50% for fluorescein. We hypothesize that this apparent plateauing behavior is due to anatomical barriers that inhibit coverage in the inferior hemisphere, especially for particles (Chiang et al, 2016b). …”

Section: Resultsmentioning

confidence: 99%

“…For example, glaucoma treatment requires localization near the ciliary body, which is near the site of microneedle injection (Chiang et al, 2016a; Kim et al, 2014b); while noninfectious posterior uveitis requires spreading throughout the SCS (Goldstein, 2015). Deposition within the SCS can be geographically controlled so as to target diseased tissues while sparing non-diseased tissues (Chiang et al, 2016b; Einmahl et al, 2002; Kim et al, 2014a; Kim et al, 2015; Tyagi et al, 2013). In particular, the area of particle spread can be controlled with different excipient formulations (Kim et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…A microneedle (750 μm in length, 33-gauge; kindly provided by Clearside Biomedical, Alpharetta, GA) attached to a 250 μL glass chromatography syringe (National Scientific, Rockwood, TN) was used to make injections. Injections were performed 3 mm posterior to the limbus at the 12 o’clock position (superior) to be as far as possible from anatomical barriers created by the long posterior ciliary artery that impede circumferential flow(Chiang et al, 2016b). …”

Section: Methodsmentioning

confidence: 99%

“…After SCS injection and freezing, eyes were prepared to assess the 2D spread of particles and fluorescein, as described previously(Chiang et al, 2016b; Kim et al, 2015; Patel et al, 2012). The frozen eye was sliced open from the limbus to the posterior pole to generate eight approximately equidistant scleral flaps.…”

Section: Methodsmentioning

confidence: 99%

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Distribution of particles, small molecules and polymeric formulation excipients in the suprachoroidal space after microneedle injection

Chiang

Venugopal

Edelhauser

et al. 2016

Experimental Eye Research

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The purpose of this work was to determine the effect of injection volume, formulation composition, and time on circumferential spread of particles, small molecules and polymeric formulation excipients in the suprachoroidal space (SCS) after microneedle injection into New Zealand White rabbit eyes ex vivo and in vivo. Microneedle injections of 25–150 μL Hank’s Balanced Salt Solution (HBSS) containing 0.2 μm red-fluorescent particles and a model small molecule (fluorescein) were performed in rabbit eyes ex vivo, and visualized via flat mount. Particles with diameters of 0.02 – 2 μm were co-injected into SCS in vivo with fluorescein or a polymeric formulation excipient: fluorescein isothiocyanate (FITC)-labeled Discovisc or FITC-labeled carboxymethyl cellulose (CMC). Fluorescent fundus images were acquired over time to determine area of particle, fluorescein and polymeric formulation excipient spread, as well as their co-localization. We found that fluorescein covered a significantly larger area than co-injected particles when suspended in HBSS, and that this difference was present from 3 min post-injection onwards. We further showed that there was no difference in initial area covered by FITC-Discovisc and particles; the transport time (i.e., the time until the FITC-Discovisc and particle area began dissociating) was 2 d. There was also no difference in initial area covered by FITC-CMC and particles; the transport time in FITC-CMC was 4 d. We also found that particle size (20 nm – 2 μm) had no effect on spreading area when delivered in HBSS or Discovisc. We conclude that (i) the area of particle spread in SCS during injection generally increased with increasing injection volume, was unaffected by particle size and was significantly less than the area of fluorescein spread, (ii) particles suspended in low-viscosity HBSS formulation were entrapped in the SCS after injection, whereas fluorescein was not and (iii) particles co-injected with viscous polymeric formulation excipients co-localized near the site of injection in the SCS, continued to co-localize while spreading over larger areas for 2 – 4 days, and then no longer co-localized as the polymeric formulation excipients were cleared within 1 – 3 weeks and the particles remained largely in place. These data suggest that particles encounter greater barriers to flow in SCS compared to molecules and that co-localization of particles and polymeric formulation excipients allow spreading over larger areas of the SCS until the particles and excipients dissociate.

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Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Distribution of particles, small molecules and polymeric formulation excipients in the suprachoroidal space after microneedle injection

Chiang

Venugopal

Edelhauser

et al. 2016

Experimental Eye Research

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Microneedles for Ocular Drug Delivery and Targeting: Challenges and Opportunities

Tekko

Singh

2018

Microneedles for Drug and Vaccine Delivery and Patient Monitoring

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Microfabricated Drug Delivery Devices: Design, Fabrication, and Applications

Zhang

Jackson

Chiao

2017

Adv Funct Materials

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Microfabrication technology has enabled the development of novel controlled-release devices that possess an integration of structural, mechanical, and perhaps electronic features, which may address challenges associated with conventional delivery systems. In this feature article, microfabricated devices are described in terms of materials, mechanical design, working principles, and fabrication methods, all of which are key features for production of multifunctional, highly effective drug delivery systems. In addition, the current status and future prospects of different types of microfabricated devices for controlled drug delivery are summarized and analyzed with an emphasis on various routes of administration including ocular, oral, transdermal, and implantable systems. It is likely that microfabrication technology will continue to offer new, alternative solutions to design advanced and sophisticated drug delivery devices that promise to significantly improve medical care.

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Circumferential flow of particles in the suprachoroidal space is impeded by the posterior ciliary arteries

Cited by 40 publications

References 24 publications

Distribution of particles, small molecules and polymeric formulation excipients in the suprachoroidal space after microneedle injection

Distribution of particles, small molecules and polymeric formulation excipients in the suprachoroidal space after microneedle injection

Microneedles for Ocular Drug Delivery and Targeting: Challenges and Opportunities

Microfabricated Drug Delivery Devices: Design, Fabrication, and Applications

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