Polyester nanocapsules as new topical ocular delivery systems for cyclosporin A.
OBJECTIVE
Nanocapsules composed of an oily core (Migliol 840) (MG) surrounded by a poly-epsilon-caprolactone (PECL) coat were evaluated as potential vehicles for the topical ocular administration of cyclosporin A (CyA).


METHODS
A 2(3) experimental factorial design was applied to optimize the coating of the oily nanodroplets by a solvent displacement technique and to encapsulate a high dose of CyA. The variables investigated were: volume of oil (MG), amount of polymer (PECL), and volume of the organic solvent (acetone) used to dissolve the polymer.


RESULTS
Nanocapsules had a mean size in the range of 210-270 nm, a negative zeta potential (between -55 and -60 mV) and a maximum loading capacity of 50% (CyA/PECL ratio). These highly loaded nanocapsules displayed a thick spongeous polymer coating around the oily nanodroplets. The corneal levels of CyA were up to 5 times higher for the encapsulated CyA than for the oily solution of CyA. In addition, these levels remained significantly higher than those of the control group (oily solution) for up to 3 days. Furthermore, the area-under-the-curve (AUC) values were significantly increased for the encapsulated CyA (319.98) with respect to the oily control (74.34).


CONCLUSIONS
The CyA-loaded nanocapsules are shown to be interesting vehicles for the improvement of the ocular penetration of CyA.
Calvo
P
P
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Spain.
Sanchez
A
A
Martinez
J
J
Lopez
M I
MI
Calonge
M
M
Pastor
J C
JC
Alonso
M J
MJ
D000287:Administration, Topical; D000818:Animals; D002214:Capsules; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003315:Cornea / Q000378:metabolism*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D009883:Ophthalmic Solutions; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage; D011817:Rabbits
D002214:Capsules; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D011091:Polyesters; C016240:polycaprolactone; D016572:Cyclosporine