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Hannah McMillan, Steven Fallows, Thakur Raghu Singh, David Jones; A minimally invasive and localised intra-scleral delivery of drug-loaded thermoresponsive polymeric implants to treat posterior ocular diseases. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5043.
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This study evaluates minimally invasive hollow microneedles (HMNs) to deliver thermoresponsive-based intrascleral implants for sustained drug release.
Gel formulations containing thermo-responsive polymer i.e. poloxamer, loaded with fluorescein sodium (FNa), were evaluated for rheological analysis, syringeability through HMNs & penetration forces of HMNs into rabbit sclera. Visualisation of gel-based implant formation in sclera and scleral recovery were also determined, using optical coherence tomography (OCT). Ex vivo FNa release following intrascleral delivery of gels was tested in Franz-diffusion cells. HMNs were fabricated from different hypodermic needles (i.e. 26G, 29G & 30G) that were adjusted to different heights (i.e., 400, 500 or 600 µm).
Gelation temperatures of poloxomer formulations ranged from 20.8 - 30.7°C, which showed Newtonian behaviour at 20°C and pseudoplastic (shear-thinning) behaviour at 37°C. The maximum force and work required in expelling gels from HMNs increased with poloxamer concentration, with volume of gel expelled (30, 50 or 100 µL) and with decrease in needle aperture (26G to 30G). Nevertheless low force (i.e., 0.123 - 2.021 N) & work (0.139 - 6.000 Ns) was required across all variables tested. Forces required to penetrate the scleral tissue correlated well with increasing needle size and depth of penetration (equator; 0.549 - 1.159 N, anterior; 0.710 - 1.346 N, posterior; 0.905 - 1.589 N). OCT studies revealed that HMNs has successfully able to penetrate to the required depth and allowed intrascleral injection of 50 µL of gel. Recovery of the sclera following injection correlated well with penetration depth. FNa release was 80.88- 87.56%, 70.33 - 75.02% and 52.86 - 60.63%, respectively after 24 h, when 50 µL of FNa-poloxamer gels were injected at a depth of 400 µm, 500 µm and 600 µm, intrasclerally.
This study has indicated the potential for sustained delivery when using thermo-responsive polymers injected intrasclerally via HMNs and also scleral recovery and implant visualization. Results suggest that this method may offer a minimally invasive means of treating posterior segment diseases.
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