Influence of preparation conditions on acyclovir-loaded poly-d,l-lactic acid nanospheres and effect of PEG coating on ocular drug bioavailability

Purpose. The evaluation of nanosphere colloidal suspensions containingacyclovir as potential ophthalmic drug delivery systems was carriedout. The influence of polymer molecular weight and type andconcentration of various surfactants on nanosphere properties wasstudied. The ocular pharmacokinetics of acyclovir-loaded nanoparticleswas evaluated in vivo and compared with an aqueous suspensionof the free drug.Methods. Nanospheres were made up of poly-d,l-lactic acid (PLA).The colloidal suspension was obtained by a nanoprecipitation process.The surface properties of PLA nanospheres were changed bythe incorporation of pegylated 1,2-distearoyl-3-phosphatidylethanolamine.The mean size and zeta potential of the nanospheres weredetermined by light scattering analysis. The acyclovir loading capacityand release were also determined. In vivo experiments were carriedout on male New Zealand rabbits. The ocular tolerability of PLAnanospheres was evaluated by a modified Draize test. The aqueoushumor acyclovir levels were monitored for 6 h to determine thedrug’s ocular bioavailability for the various formulations.Results. A reduction of the mean size and a decrease of the absolutezeta potential of PLA nanospheres resulted from increasing the surfactantconcentration. The higher the polymer molecular weight, thesmaller the nanosphere mean size. PEG-coated and uncoated PLAnanospheres showed a sustained acyclovir release and were highlytolerated by the eye. Both types of PLA nanospheres were able toincrease the aqueous levels of acyclovir and to improve the pharmacokineticsprofile, but the efficacy of the PEG-coated nanosphereswas significantly higher than that of the simple PLA ones.Conclusions. PEG-coated PLA nanospheres can be proposed as apotential ophthalmic delivery system for the treatment of ocular viralinfections.