Suprachoroidal Drug Delivery to the Back of the Eye Using Hollow Microneedles

PURPOSE: In this work, we tested the hypothesis that microneedles provide a minimally invasive method to inject particles into the suprachoroidal space for drug delivery to the back of the eye. METHODS: A single, hollow microneedle was inserted into the sclera, and infused nanoparticle and microparticle suspensions into the suprachoroidal space. Experiments were performed on whole rabbit, pig, and human eyes ex vivo. Particle delivery was imaged using brightfield and fluorescence microscopy as well as microcomputed tomography. RESULTS: Microneedles were shown to deliver sulforhodamine B as well as nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig, and human eyes. Volumes up to 35 μL were administered consistently. Optimization of the delivery device parameters showed that microneedle length, pressure, and particle size played an important role in determining successful delivery into the suprachoroidal space. Needle lengths of 800–1,000 μm and applied pressures of 250–300 kPa provided most reliable delivery. CONCLUSIONS: Microneedles were shown for the first time to deliver nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig and human eyes. This shows that microneedles may provide a minimally invasive method for controlled drug delivery to the back of the eye

In Vivo Ocular Fluorophotometry: Delivery of Fluoresceinated Dextrans via Transscleral Diffusion in Rabbits

Fluoresceinated dextrans up to 70 kDa in size were delivered to the rabbit posterior retina and choroid using sub-Tenon injections. Intraocular fluorescence was monitored in vivo with noninvasive ocular fluorophotometry

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

Topical drug delivery to the eye is subject to low bioavailability because of the rapid clearance of drug from the ocular surface. In this study, the authors prepared mucoadhesive microparticles formulated in a rapidly dissolving tablet to achieve sustained drug delivery to the eye

Targeted allergen-specific immunotherapy within the skin improves allergen delivery to induce desensitization to peanut

Aim: Epicutaneous immunotherapy (EPIT) with peanut has been demonstrated to be safe but efficacy may be limited by allergen uptake through the skin barrier. To enhance allergen uptake into the skin, the authors used peanut-coated microneedles and compared them with EPIT in a peanut allergy mouse model. Methods: Sensitized mice were treated with peanut-coated microneedles or peanut-EPIT and then challenged with peanut to determine protection. Results: Treatment with peanut-coated microneedles was safe and showed enhanced desensitization to peanut compared with peanut-EPIT administered via a similar schedule. Protection was associated with reduced Th2 immune responses and mast cell accumulation in the intestine. Conclusion: Peanut-coated microneedles have the potential to present a safe method of improving allergen delivery for cutaneous immunotherapy. </jats:p

Supplementary Material: Targeted allergen-specific immunotherapy within the skin improves allergen delivery to induce desensitization to peanut

Supplementary Figure 1. Peanut-coated microneedles do not cause reactivity in peanut-sensitized mice. Sensitized mice were treated with PBS, peanut (PN-EPIT), OVA-coated MNs (OVA-MN) or peanut-coated MNs (PN-MN). Mice were monitored for symptoms of allergic reactions following application of immunotherapy. (A) Temperature change was monitored for 120 minutes after application. (B) Mice were monitored for clinical symptoms of allergic reactions for 120 minutes after application with no symptoms noted. (C) Levels of MCPT-1 in the serum 60 min after application were determined by ELISA. N =10 mice/group. Data are presented as mean ± SEM. Supplementary Figure 2. Investigation of a time course of PN-EPIT in peanut-sensitized mice. Sensitized mice were treated epicutaneously with PBS (sham) or peanut (PN-EPIT). PN-EPIT durations of 5, 8 and 12 weeks were tested. Mice were challenged orally with peanut and reactivity was determined following the final oral challenge. (A) Mice were monitored for clinical symptoms of allergic reactions for 60 minutes after challenge. (B) Temperature change was monitored for 60 minutes after application. (C) Levels of MCPT-1 in the serum 60 min after application were determined by ELISA. Data are presented as mean ± SEM. *p < 0.05, **p < 0.01 and ***p Supplementary Figure 3. Quantification of peanut-specific IgE from IgG-depleted serum. Serum pools were generated by combining samples collected at the end of the study. Two serum samples were combined to generate each sera pool. IgG was depleted from each sera pool, and peanut-specific IgE antibody titers were determined in the IgG-depleted serum. N=5 pools per group. Data are presented as mean ± SEM. *p </div