Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 109, Issue -, Pages 224-235Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2016.10.015
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- National Center for Research Resources [1R01EY022120-01A1, P20 GM104932]
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Purpose: The objective of the present study was to formulate indomethacin (IN)-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) and to investigate their potential use in topical ocular delivery. Methods: IN SLNs (0.1% w/v) and NLCs (0.8% w/v) were prepared, characterized and evaluated. Their in vitro. release and flux profiles across the cornea and sclera-choroid-RPE (trans-SCR) tissues and in vivo ocular tissue distribution were assessed. Furthermore, chitosan chloride (CS) (mol. wt. < 200 kDa), a cationic and water-soluble penetration enhancer, was used to modify the surface of the SLNs, and its effect was investigated through in vitro transmembrane penetration and in vivo distribution tissue studies. Results: For the IN-SLNs, IN-CS-SLNs and IN-NLCs, the particle size was 226 +/- 5, 265 +/- 8, and 227 +/- 11 nm, respectively; the zeta potential was -22 +/- 0.8, 27 +/- 1.2, and -12.2 +/- 2.3 mV, respectively; the polydispersity index (PDI) was 0.17, 0.30, and 0.23, respectively; and the entrapment efficiency (EE) was 81 +/- 0.9, 91.5 +/- 3.2 and 99.8 +/- 0.2%, respectively. The surface modification of the SLNs with CS increased the ocular penetration of IN. The NLCs maintained significantly higher IN concentrations in all ocular tissues tested compared to the other formulations evaluated in vivo. Conclusion: The results suggest that lipid-based particulate systems can serve as viable vehicles for ocular delivery. The NLC formulations demonstrated increased drug loading capability, entrapment and delivery to anterior and posterior segment ocular tissues. (C) 2016 Elsevier B.V. All rights reserved.
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