Hydrocortisone delivery to healthy and inflamed eyes using a micellar polysorbate 80 solution or albumin nanoparticles
Zimmer, A.K.; Maincent, P.; Thouvenot, P.; Kreuter, J.
International Journal Of Pharmaceutics (amsterdam). 110(3): 211-222
Hydrocortisone was loaded onto albumin nanoparticles by sorption. Two systems were tested, one comprised of a 0.03% saturated drug solution, the other of a 0.2% micellised drug solution. In both cases 45-70% of the originally available drug was bound to the carrier surface. The systems were further tested by measuring the in vitro transport of radiolabelled hydrocortisone through porcine cornea. Nanoparticles led to sustained drug transport through the cornea. The distribution of both 0.2% hydrocortisone preparations (nanoparticles and solution) was then evaluated under in vivo conditions in healthy and inflamed eyes of rabbits. In all tissues the level of drug was higher in the inflamed than in the healthy eye due to increased cell permeability as a result of inflammatory processes. The application of nanoparticles led to lower hydrocortisone tissue concentrations than the reference solution due to the strong binding of hydrocortisone onto the particle system and the resulting slow release. An exception occurred with the reference solution in the conjunctiva, as less drug was found in the inflamed than in the normal tissue, since enhanced lacrimation led to increased drug drainage. In contrast, the corresponding nanoparticle preparation was more efficiently retained at the inflamed than at the normal conjunctiva. Consequently, in the inflamed eye, hydrocortisone-loaded nanoparticles enabled targeting to the precorneal area away from the inner segments of the eye.