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Galantamine, an acetylcholinesterase inhibitor used in the treatment of patients with Alzheimer's disease, increases neurogenesis and produces a neuroprotective effect. Previous studies from our group have indicated that galantamine improves recovery after spinal cord injury (SCI). However, the need of repeated dosing and cholinergic side effects of galantamine are the major hurdles for the optimum usage of this drug. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers such as polyseters, which sustain the release of encapsulated drugs. Electrospraying is acknowledged to be an important technique for the preparation of nanoparticles. Astrocytes are important players in the formation of the scar that impedes regeneration after SCI, and they express cholinergic receptors, which can be indirectly modulated by galantamine.

Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados

The objective of this study has been to develop a drug delivery system using poly (lactic-co-glycolic acid) (PLGA) microparticles with galantamine and test their biocompatibility in astrocyte cultures from rat cortex.

Galantamine containing microparticles were produced by electrospraying 4% PLGA polymer solutions with three different drug proportions (1%, 5% and 10%). The parameters used for the electrospraying were: flow rate 0.5 ml / h, voltage of 23-26kV and 9 cm of distance from the needle to the collector plate. The morphology of the particles was evaluated by Scanning Electron Microscopy (SEM) and the diameter and zeta potential of the particle suspension was measured by the Zetasizer. Astrocytes isolated from the cortex of Wistar rat pups were incubated with the different microparticles and the cellular viability and cytotoxicity were analyzed by the WST8 and LDH assay, respectively. For morphological analysis, the cell cultures were labeled with GFAP (glial fibrillary acidic protein) and DAPI (nuclear marker).

The particle morphology varied according to the galantamine concentration used, as can be seen by the MEV analysis. The zeta potential of the particles was of -41.5 ± 4.9 mV for particles with only 4% PLGA and -28,03 ± 3,0 mV, -14 , 33 ± 0.15 mV and -33.78 ± 2.9 mV for particles containing 1%, 5%, and 10% of galantamine, respectively. The average particle diameter was 434.73 ± 49.67 nm for particles with 4% PLGA alone, and 835.1 ± 69.53 nm, 762 ± 338.03 nm and 576.45 ± 235.07 nm for the PLGA particles with 1%, 5% and 10% of galantamine, respectively. The WST8 assay showed that 4% PLGA increased astrocyte viability on day 1 (1.60 ± 0.3) as well as day 7 (2.261 ± 0.1) as compared to the controls (cells with no treatment) 0.770 ± 0.37 and 1.691 ± 0.16 on days 1 and 7, respectively. However, cell viability was lower in the 4% PLGA groups associated with 10% Galantamine on both day 1 (0.62 ± 0.14) and day 7 (1.04 ± 0.16) when compared to the groups treated with galantamine (1.15 ± 0.34 and 1.78 ± 0.14 on days 1 and 7, respectively). The LDH assay showed that the 4% PLGA particles are not cytotoxic for the cells (132.08 ± 2.5) when compared to the control (248.893 ± 21.9).

Considerações Finais/Final considerations/Consideraciones finales

With the present study, it can be concluded that 4% PLGA microparticles present good biological activity with astrocytes and are non-cytotoxic, and when associated with galantamine, decrease astrocyte viability, being, therefore, a possible strategy to reduce glial scaring in the future.

Palavras-chave/Key words/Palabras clave

astrocytes, galantamine, electrospraying, microparticles, glial scar.




VICTORIA TOMAZ, Laura Elena Sperling, Flávia Prezzi, Márcia Rosângela Wink, Patrícia Pranke