Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles

• Published in: European journal of pharmaceutics and biopharmaceutics 2015-09, Vol.95 (Pt B), p.398-406
• Main Authors: Kim, Yoo Chun, Oh, Kyung Hee, Edelhauser, Henry F., Prausnitz, Mark R.
• Format: Article
• Language: English
• Subjects: Animals; Chemistry, Pharmaceutical - methods; Choroid - metabolism; Ciliary Body - metabolism; Drug Delivery Systems; Eye; Hyaluronic Acid - chemistry; Microneedles; Microspheres; Nanoparticles; Needles; Ocular drug delivery; Particle formulation; Polymers - chemistry; Rabbits; Sclera - metabolism; Suprachoroidal space; Time Factors
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2015.05.020

[Display omitted] In this work, we tested the hypothesis that particles injected into the suprachoroidal space can be localized at the site of injection or broadly distributed throughout the suprachoroidal space by controlling polymeric formulation properties. Single hollow microneedles were inserted into the sclera of New Zealand White rabbits and injected non-biodegradable fluorescently tagged nanoparticles and microparticles suspended in polymeric formulations into the suprachoroidal space of the eye. When formulated in saline, the particles were distributed over 29–42% of the suprachoroidal space immediately after injection. To spread particles over larger areas of the choroidal surface, addition of hyaluronic acid to make moderately non-Newtonian solutions increased particle spread to up to 100% of the suprachoroidal space. To localize particles at the site of injection adjacent to the ciliary body, strongly non-Newtonian polymer solutions localized particles to 8.3–20% of the suprachoroidal space, which exhibited a small increase in area over the course of two months. This study demonstrates targeted particle delivery within the suprachoroidal space using polymer formulations that spread particles over the whole choroidal surface or localized them adjacent to the ciliary body after injection.