Luschmann, Christoph and Tessmar, Joerg and Schoeberl, Simon and Strauss, Olaf and Framme, Carsten and Luschmann, Karl and Goepferich, Achim (2013) Developing an in situ nanosuspension: A novel approach towards the efficient administration of poorly soluble drugs at the anterior eye. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 50 (3-4). pp. 385-392. ISSN 0928-0987, 1879-0720
Full text not available from this repository. (Request a copy)Abstract
With about 50-60 million cases in the US alone, dry eye disease represents a severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a causal therapy. However, CsA is not sufficiently water soluble to be administrated via simple eye drops. We developed an in situ nanosuspension (INS) as a novel approach towards the administration of CsA to the cornea. It precipitates upon contact with the tear fluid and creates CsA nanoparticles that enter the cornea and release the drug by dissolution. We selected two liquid poly(ethylene glycols) (PEG) that dissolve CsA and create nanoparticles by precipitation of CsA upon water contact. Aqueous solutions of PEG and Solutol, a non-ionic surfactant, were well tolerated by primary human epithelial cells in vitro. To determine the critical water content needed for a precipitation, the solubility of CsA was investigated in quaternary systems of drug, solvent, surfactant and water. The best INS formulation showed a particle size of 505 +/- 5 nm, a polydispersity index (PdI) of 0.23 +/- 0.03 and a neutral zeta potential of -0.07 +/- 0.05 mV. After single administration to porcine eyes in vitro, 3165 +/- 597 ng(CsA)/g(cornea) were detected in corneal tissue, while the levels of Restasis(R) a commercial formulation were, with 545 +/- 137 ng(CsA)/g(cornea), significantly lower (P < 0.01). These results demonstrate that an INS is a promising, novel approach towards the causal treatment of inflammatory diseases at the anterior eye. (C) 2013 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TOPICAL CYCLOSPORINE-A; OCULAR DELIVERY-SYSTEMS; DRY EYE; KERATOCONJUNCTIVITIS SICCA; SJOGRENS-SYNDROME; DISEASE; PENETRATION; VEHICLE; CORNEA; DOGS; Cyclosporin A; Nanosuspension; Poly(ethylene glycol); Solutol; Precipitation; Anterior eye |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2020 07:44 |
| Last Modified: | 26 Mar 2020 07:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15661 |
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