Memantine loaded PLGA PEGylated nanoparticles for Alzheimer's disease: in vitro and in vivo characterization.

BACKGROUND: Memantine, drug approved for moderate to severe Alzheimer's disease, has not shown to be fully effective. In order to solve this issue, polylactic-co-glycolic (PLGA) nanoparticles could be a suitable solution to increase drug's action on the target site as well as decrease adverse effects. For these reason, Memantine was loaded in biodegradable PLGA nanoparticles, produced by double emulsion method and surface-coated with polyethylene glycol. MEM-PEG-PLGA nanoparticles (NPs) were aimed to target the blood-brain barrier (BBB) upon oral administration for the treatment of Alzheimer's disease. RESULTS: The production parameters were optimized by design of experiments. MEM-PEG-PLGA NPs showed a mean particle size below 200 nm (152.6 ± 0.5 nm), monomodal size distribution (polydispersity index, PI < 0.1) and negative surface charge (- 22.4 mV). Physicochemical characterization of NPs confirmed that the crystalline drug was dispersed inside the PLGA matrix. MEM-PEG-PLGA NPs were found to be non-cytotoxic on brain cell lines (bEnd.3 and astrocytes). Memantine followed a slower release profile from the NPs against the free drug solution, allowing to reduce drug administration frequency in vivo. Nanoparticles were able to cross BBB both in vitro and in vivo. Behavioral tests carried out on transgenic APPswe/PS1dE9 mice demonstrated to enhance the benefit of decreasing memory impairment when using MEM-PEG-PLGA NPs in comparison to the free drug solution. Histological studies confirmed that MEM-PEG-PLGA NPs reduced ß-amyloid plaques and the associated inflammation characteristic of Alzheimer's disease. CONCLUSIONS: Memantine NPs were suitable for Alzheimer's disease and more effective than the free drug.

Estudio de correlación entre la concentración de antígeno de superficie y la carga viral del virus de la hepatitis B en una población negativa para el antígeno e / Correlation between hepatitis B surface antigen serum levels and viral load in an hepatitis B e antigen negative population

Introducción. La posible falta de correlación entre la concentración de HbsAg del virus de la hepatitis B y la carga viral observada en nuestro hospital, y la gran controversia existente en torno a este aspecto, ha motivado el presente estudio. Adicionalmente, se realizan estudios de eficiencia diagnóstica de la cuantificación de HbsAg para verificar la utilidad real de la introducción de esta determinación en nuestro laboratorio. Métodos. Se han usado 150 muestras de portadores crónicos del virus. Los individuos HbeAg negativos se dividen en 4 grupos: (HbsAg < 1.000 UI/mL [subgrupo 1], HbsAg > 1.000 UI/mL [subgrupo 2], DNA < 2.000 UI/mL [subgrupo 3], DNA > 2.000 UI/mL [subgrupo 4]). Tanto la cuantificación de HbsAg como la determinación cualitativa de HbeAg se han realizado mediante inmunoanálisis quimioluminiscente en el analizador Architect® i2000SR (Abbott Laboratories, Sligo, Irlanda). La carga viral se ha cuantificado mediante PCR a tiempo real (RT-PCR) (Cobas Ampliprep/Cobas TaqMan® de Roche Diagnostics) (Manheim, Alemania). Los estudios de correlación se han realizado mediante la prueba de Spearman utilizando el programa estadístico MedCalc®. Resultados. Los coeficientes de correlación obtenidos han sido: grupo total HbeAg negativo (r=0,322; p=0,0002); subgrupo 1 (r=0,501; p=0,0001); subgrupo 2 (r=-0,105; p=0,362); subgrupo 3 (r=0,275; p=0,0052); subgrupo 4 (r=0,299; p=0,092). Conclusión. Se ha observado una modesta pero significante correlación entre las concentraciones séricas de HbsAg y los valores de DNA-VHB en individuos HbeAg negativos (AU)

Background. Possible lack of correlation observed among serum hepatitis B surface antigen (HbsAg) concentration results and viral load in our hospital, and the great controversy surrounding this aspect in the literature, has motivated this study. Additionally, diagnostic efficiency analysis of quantitative HbsAg measurement are done in order to verify the real usefulness of the introduction of this test in our laboratory. Methods. 150 hepatitis B chronic carriers samples have been used. Negative HbeAg individuals were divided in four groups (HbsAg < 1,000 UI/mL [subgroup 1], HbsAg > 1,000 UI/mL [subgroup 2], DNA < 2,000 UI/mL [subgroup 3], DNA > 2,000 UI/mL [subgroup 4]). Both quantitative HbsAg and qualitative HbeAg have been performed by a chemiluminiscent immunoassay from Architect® i2000SR analyzer (Abbott Laboratories, Sligo, Ireland). Viral load has been quantified by real time polymerase chain reaction (RT-PCR) (Cobas Ampliprep/Cobas TaqMan® from Roche Diagnostics) (Manheim, Germany). Correlation studies have been performed by the Spearman test. Statistical analysis have been performed using MedCalc® software. Results. Correlation coeficients obtained in this study have been: Total negative HbeAg group (r=0.322; p=.0002); subgroup 1 (r=0.501; p=.0001); subgroup 2 (r=-0.105; p=.362); subgroup 3 (r=0.275; p=.0052); subgroup 4 (r=0.299; p=.092). Conclusion. Modest but significant correlation between HbsAg levels and VHB-DNA values in negative HbeAg individuals has been observed (AU)