Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 101, Issue 3, Pages 1040-1049Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.22813
Keywords
nanostructured lipid carriers; coating; chitosan; biomaterials; solubility; ocular drug delivery; permeability; transcorneal permeation; precorneal retention; ocular irritation
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The objective of this study was to propose novel surface-modified nanostructured lipid carriers with partially deacetylated water-soluble chitosan (NLCPDSC) as an efficient ocular delivery system to improve its transcorneal penetration and precorneal retention. PDSC with a deacetylation degree of around 50% was synthesized using an improved method. NLC loaded with flurbiprofen (FB) were prepared by melt emulsification method. They presented spherical morphology under both transmission electron microscope and scanning electron microscope. After coating with 0.15% (w/v) PDSC solution, the NLC showed a coreshell structure and a reversed zeta potential. The enhanced transcorneal penetration of the coated NLC was evaluated using isolated rabbit corneas, with significantly increased apparent permeability coefficient being 1.40- and 1.75-fold of the NLC and FB phosphate solution (FB-sol; p < 0.05), respectively. Precorneal retention assessed by gamma scintigraphy in vivo showed that the area under the remaining activitytime curve of the PDSC-coated formulation was 1.3-fold of the NLC and 2.4-fold of FB-sol. Moreover, in vivo ocular tolerance study indicated that there was no difference in irritation between the coated and noncoated NLC. In conclusion, novel NLC demonstrate high potential for ocular drug delivery. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:10401049, 2012
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