Sýklódextrín örkorn fyrir markbundna lyfjagjöf í augum - verkefni lokið

Fréttatilkynning verkefnisstjóra


Previously we discovered that drug/cyclodextrin complexes can self-assemble in aqueous solutions to form nanoparticles (aggregates). The diameter of these nanoparticles is about 100 nm. In this project the nanoparticles were allowed to selfassemble further to form small microparticles with limited water solubility. 

Heiti verkefnis: Sýklódextrín örkorn fyrir markbundna lyfjagjöf í augum
Verkefnisstjóri: Þorsteinn Loftsson, Háskóla Íslands

Tegund styrks: Verkefnisstyrkur
Styrkár: 2013-2015
Fjárhæð styrks: 17,5 millj. kr. alls
Tilvísunarnúmer Rannís:  130031

The microparticles (diameter about 2 μm or 2000 nm) formed micro-suspension in aqueous media. Studies have shown that after topical administration to the eye the  drug/cyclodextrin microparticles adhere to conjunctiva where they slowly disassemble to form nanoparticles with diameter of about 100 nm and then individual drug/cyclodextrin complexes that finally release the drug into the eye's cornea and sclera. The microparticles allow sustained drug delivery, the nanoparticles enhance rug delivery through the eye's mucus layer and the drug/cyclodextrin complexes maintain high concentration of dissolved drug in the tear fluid. The overall effect is enhanced drug delivery from the eye surface into the eye. In this project γ-cyclodextrin (γCD) which has GRAS (generally recognized as safe) recognition in food and drug industry was used. Formation of irbesartan/γCD, telmisartan/γCD and hydrocortisone/γCD were studies as well as cyclodextrin complexes of amphotericin B and dexamethasone. Aqueous eye drop microsuspension containing irbesartan/γCD complexes was developed and tested in vitro. One Ph.D. student has for three years worked full time on this project. The student will defend her thesis later this year. It has resulted in 6 publications in peerreviewed journals and numerous lectures and poster presentations at scientific meetings. The developed irbesartan/γCD eye drops will be tested in vivo in animals and, if everything goes well, will undergo clinical testing in humans.

List of publications (and manuscripts to be published) in peer-reviewed journals:

1. P. Jansook, C. Muankaew, E. Stefánsson, T. Loftsson, Development of eye drops containing antihypertensive drugs: formulation of aqueous irbesartan/γCD eye drops, Pharm. Dev. Technol. 20(5), 626-632 (2015).

2. Z. Fülöp, A. Balogh, P. Saokham, P. Jansook, T. Loftsson, Formation and stability assessment of self-assembled nanoparticles from large Mw chitosan and sulfobutylether-β-cyclodextrin, J. Drug Deliv. Sci. Technol. 30, 478-485 (2015).

3. C. Muankaew, P. Jansook, E. Stefánsson, T. Loftsson, Effect of γ-cyclodextrin on solubilization and complexation of irbesartan: influence of pH and excipients, Int. J. Pharm. 474, 80-90 (2014).

4. P. Jansook, W. Pichayakorn, C. Muankaew, T. Loftsson, Cyclodextrin-poloxamer aggregates as nanocarriers in eye drop formulations: dexamethasone and amphotericin B, Drug. Dev. Ind. Pharm. in print (2016).

5. C. Muankaew, P. Jansook, T. Loftsson, Effect of γ-cyclodextrin on permeation of lipophilic drugs: application of cellophane/fused octanol membrane, (manuscript). 

6. T. Loftsson, Self-assembled cyclodextrin nanoparticles and drug delivery, J. Incl. Phenom. Macroc. Chem. 80, 1-7 (2014).  

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