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Influence of Preparation Conditions on Acyclovir-Loaded Poly-d,l-Lactic Acid Nanospheres and Effect of PEG Coating on Ocular Drug Bioavailability

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Abstract

Purpose. The evaluation of nanosphere colloidal suspensions containing acyclovir as potential ophthalmic drug delivery systems was carried out. The influence of polymer molecular weight and type and concentration of various surfactants on nanosphere properties was studied. The ocular pharmacokinetics of acyclovir-loaded nanoparticles was evaluated in vivo and compared with an aqueous suspension of 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 by the incorporation of pegylated 1,2-distearoyl-3-phosphatidylethanol- amine. The mean size and zeta potential of the nanospheres were determined by light scattering analysis. The acyclovir loading capacity and release were also determined. In vivo experiments were carried out on male New Zealand rabbits. The ocular tolerability of PLA nanospheres was evaluated by a modified Draize test. The aqueous humor acyclovir levels were monitored for 6 h to determine the drug's ocular bioavailability for the various formulations.

Results. A reduction of the mean size and a decrease of the absolute zeta potential of PLA nanospheres resulted from increasing the surfactant concentration. The higher the polymer molecular weight, the smaller the nanosphere mean size. PEG-coated and uncoated PLA nanospheres showed a sustained acyclovir release and were highly tolerated by the eye. Both types of PLA nanospheres were able to increase the aqueous levels of acyclovir and to improve the pharmacokinetics profile, but the efficacy of the PEG-coated nanospheres was significantly higher than that of the simple PLA ones.

Conclusions. PEG-coated PLA nanospheres can be proposed as a potential ophthalmic delivery system for the treatment of ocular viral infections.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Catania, I-95125, Catania, Italy

    Claudia Giannavola, Donatella Paolino & Giovanni Puglisi

  2. Bausch & Lomb-Fidia Oftal Research Laboratories, I-95127 Catania, I-95125, Catania, Italy

    Claudio Bucolo & Adriana Maltese

  3. Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, I-41100, Modena, Italy

    Maria Angela Vandelli

  4. Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, California, 90089-9121

    Vincent H. L. Lee

  5. Department of Pharmacobiological Sciences, University of Catanzaro “Magna Græcia,”, I-88021, Roccelletta di Borgia (CZ), Italy

    Massimo Fresta

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  1. Claudia Giannavola
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Correspondence to Massimo Fresta.

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Giannavola, C., Bucolo, C., Maltese, A. et al. Influence of Preparation Conditions on Acyclovir-Loaded Poly-d,l-Lactic Acid Nanospheres and Effect of PEG Coating on Ocular Drug Bioavailability. Pharm Res 20, 584–590 (2003). https://doi.org/10.1023/A:1023290514575

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