Polyhydroxyethylaspartamide-based micelles for ocular drug delivery

In this paper three copolymers of polyhydroxyethylaspartamide (PHEA), bearing in the side chains polyethylene glycol (PEG) and/or hexadecylamine (C16) (PHEA-PEG, PHEA-PEG-C16 and PHEA-C16 respectively) have been studied as potential colloidal drug carriers for ocular drug delivery. The physical characterization of all three PHEA derivatives, using the Langmuir trough (LT) and micellar affinity capillary electrophoresis (MACE) techniques allowed to assume that whereas alone PHEA backbone is an inert polymer with respect to the interactions with lipid membranes and drug complexation, when PHEA chains are grafted with long alkyl chains like C16 or in combination C16 chains and hydrophilic chains like PEG, copolymers with lipid membrane interaction ability and drug complexation capability are obtained.In vitro permeability studies performed on primary cultured rabbit conjunctival and corneal epithelia cells, using PHEA-C16 and PHEA-PEG-C16 as micelle carriers for netilmicin sulphate, dexamethasone alcohol and dexamethasone phosphate, demonstrated that in all cases drug loaded PHEA-C16 and PHEA-PEG-C16 micelles provide a drug permeation across ocular epithelia greater than simple drug solutions or suspensions. In particular PHEA-PEG-C16 acts as the best permeability enhancer in our experimental model. In vivo bioavailability studies conducted with PHEA-PEG-C16 micelles loaded with dexamethasone alcohol, confirmed that this system also provides a drug bioavailability greater in comparison with that obtained with water suspension of the same drug after ocular administration to rabbits.