Polycarboxylic acid nanoparticles for ophthalmic drug delivery: an ex vivo evaluation with human cornea.
In ophthalmic drug delivery, a major problem is retaining an adequate concentration of a therapeutic agent in the pre-corneal area. Polycarboxylic acid carriers such as polyacrylic acid and polyitaconic acid in sub-colloidal, nanoparticulate hydrogel form have a strong potential for sustained release of a drug in ocular delivery. Formulations have been prepared of brimonidine loaded in polycarboxylic (polyacrylic and polyitaconic) acid nanoparticles for potential ophthalmic delivery. These particles were prepared by a reverse micro-emulsion polymerization technique with sizes in the range of 50 nm. The loading efficiencies of the drug brimonidine in the particles were shown to be between 80-85% for polyacrylic acid nanoparticles and between 65-70% for polyitaconic nanoparticles. The loading efficiency was also found to be pH dependent. In a preliminary biocompatibility test, human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability, whereas polyitaconic acid nanoparticles were found to be toxic. Two-photon laser scanning microscopic studies of the fluorescently labelled polyacrylic acid nanoparticles and human cornea shows that they are adhesive on the corneal surface. The polyacrylic acid nanoparticles demonstrated a controlled release of the opthalmological drug (Brimonidine) through the human cornea as compared to that of the commercial formulation, Alphagan.
De
T K
TK
Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, SUNY at Buffalo, Buffalo, NY 14260, USA.
Bergey
E J
EJ
Chung
S J
SJ
Rodman
D J
DJ
Bharali
D J
DJ
Prasad
P N
PN
D000179:Acrylates / Q000737:chemistry / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D000068438:Brimonidine Tartrate; D002264:Carboxylic Acids; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D036103:Nanotechnology; D011108:Polymers; D011810:Quinoxalines / Q000737:chemistry / Q000493:pharmacokinetics*; D013386:Succinates / Q000737:chemistry / Q000493:pharmacokinetics
D000179:Acrylates; D000959:Antihypertensive Agents; D002264:Carboxylic Acids; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011108:Polymers; D011810:Quinoxalines; D013386:Succinates; D000068438:Brimonidine Tartrate; C036658:acrylic acid; C005229:itaconic acid