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Universidade Federal de Santa Catarina Centro de Ciências da Saúde Programa de Pós-Graduação em Farmácia

Content Provider	Semantic Scholar
Author	Amorim, Clarissa De Medeiros Córdova, Silva
Copyright Year	2011
Abstract	DEVELOPMENT AND CHARACTERIZATION OF METHOTREXATE-LOADED NANOPARTICLES. EVALUATION OF STABILITY AND VIABILITY OF CORNEAL TISSUE AFTER OCULAR ADMINISTRATION Topical drug delivery to the eye is the most common treatment of ophthalmic diseases, and the cornea provides the dominant barrier to drug transport. The potential of polymeric nanoparticles for enhancing corneal absorption after the administration of ocular drugs has been the focus of intense research in the last years. Hence, the aim of the present study was to prepare and the characterize nanocapsules and nanospheres of poly(DL-lactic acid) (PLA) and poly(DL-lactic acid)-poly(ethylene glycol) (PLA-PEG) containing antitumoral agent methotrexate (MTX) for ocular drug delivery. The nanocapsules were prepared by the interfacial deposition polymer method. The entrapment efficiency of the MTX was around 20 % for both PLA and PLA-PEG nanocapsules. Calorimetric analysis (DSC) showed a interaction between the drug and the polymer.Their physical and chemical stabilities were studied during 45 days storage at 25 and 4-8 oC and the mean particle size of all nanocapsules increased throughout this study. The nanospheres were obtained by a double emulsion (a/o/a) solvent evaporation technique, under ultrasonic stirring. PLA and PLA-PEG formulations presented mean size of 250 and 100 nm and zeta potential of -31 and -11 mV, respectively. The drug entrapment efficiency was determined by validated high-performance liquid chromatography (HPLC) method and the results obtained were 42 and 40 % for PLA and PLA-PEG, respectively. The nanospheres DSC analysis showed, as well as for the nanocapsules, a interaction between the drug and the systems. The MTX release profile from PLA and PLA-PEG nanospheres showed that 100 % of drug was released after 8 and 4 hours of study, respectively. The results demonstrated that the presence of hydrophilic PEG coating favors drug diffusion by the particles. The evaluation of interaction between nanoparticles and components of the ocular mucous, mucin and lysozyme, showed no modification in the viscosity of the mucin dispersion after incubation with both systems. However, the mean diameter and polydispersion index of PLA nanospheres increased upon incubation with lisozyme. The corneal viability tissue was examined after in vivo instillation of the blank PLA and PLA-PEG nanospheres. The rabbit corneas were removed and then stained with propidium iodide, a fluorescent dye which distinguishes viable from non-viable cells. Surface imaging of the pretreated corneas by fluorescence microscopy displayed few fluorescence signal suggesting that nanospheres administration could not be association with cellular lysis. These results suggest that PLA and PLA-PEG nanospheres present potential as ocular drug delivery system and it represents a promising alternative to the treatment of ocular diseases.
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Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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