Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.
OBJECTIVE
The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct.


METHODS
Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography.


RESULTS
Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water.


CONCLUSIONS
Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.
Attama
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AA
Institut für Pharmazeutische Technologie, Technische Universität Carolo-Wilhelmina zu Braunschweig, Braunschweig, Germany. aaattama@yahoo.com
Reichl
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Müller-Goymann
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CC
D057005:Bioengineering; D001692:Biological Transport; D002099:Cacao / Q000737:chemistry; D003315:Cornea / Q000378:metabolism*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004655:Emulsions; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D010938:Plant Oils / Q000737:chemistry*; D013999:Timolol / Q000737:chemistry / Q000493:pharmacokinetics*; D014961:X-Ray Diffraction
D003692:Delayed-Action Preparations; D004655:Emulsions; D010743:Phospholipids; D010938:Plant Oils; D013999:Timolol