Surface chemistry study of the interactions of pharmaceutical ingredients with human meibum films.
OBJECTIVE
To perform a surface chemistry study of the interactions between the benzalkonium chloride (BAC)-preserved eyedrops Travatan, the SofZia-preserved TravatanZ, and the Polyquad-preserved DuoTrav, and tear film (TF) constituents. The interactions of TF compounds with the individual preservatives, BAC, SofZia, and Polyquad, were also examined.


METHODS
Langmuir surface balance measurements were used to examine the interactions between the pharmaceuticals and films of human meibum and rabbit corneal cell lipid extracts. Surface pressure-area isocycles were used to assess the sample's capability to compress and spread during dynamic area changes. The dilatational rheologic properties of human meibum films, pure and in the presence of preservatives, were probed by stress-relaxation studies. Lipid film morphology was monitored by Brewster angle microscopy. The viability of SofZia- and Polyquad-treated Statens Seruminstitut Rabbit Cornea (SIRC) cell cultures was also evaluated.


RESULTS
The interactions between BAC-preserved eyedrops and lipids resulted in impaired lipid spread, formation of discontinuous nonuniform surface layers, and increased surface pressure-area hysteresis during compression/expansion. In contrast, TravatanZ, DuoTrav, and the individual preservatives SofZia and Polyquad proved to be safe to the lipid film structure and isothermal reversibility. The stress-relaxation experiments revealed that the viscoelastic properties of meibomian film are impaired by BAC, and remain unaffected by SofZia and Polyquad. SIRC cells' viability and capability to form confluent cellular monolayer were also maintained after exposure to SofZia and Polyquad.


CONCLUSIONS
Surface chemistry studies present criteria for preclinical in vitro molecular scale characterization of the interactions between eyedrop compounds and TF constituents.
Department of Biochemistry, Faculty of Biology, University of Sofia, Sofia, Bulgaria. ggeorg@biofac.uni-sofia.bg
Georgi A
GA
Georgiev
Norihiko
N
Yokoi
Slavyana
S
Ivanova
Rumen
R
Krastev
Zdravko
Z
Lalchev
D000328:Adult; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D003315:Cornea / Q000737:chemistry*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008537:Meibomian Glands / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000737:chemistry; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011817:Rabbits; D013499:Surface Properties / Q000187:drug effects; D013500:Surface Tension / Q000187:drug effects; D013666:Tears / Q000737:chemistry / Q000187:drug effects*; D013999:Timolol / Q000494:pharmacology; D000069557:Travoprost
D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D004338:Drug Combinations; C571754:Duotrav; D008563:Membrane Lipids; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical; D003008:Cloprostenol; D013999:Timolol; D000069557:Travoprost