RESUMEN
Background: Alzheimer's disease (AD) is the most prevalent type of dementia which has been affected to more the 44 million people globally. It is distinguished by gradually deteriorating memory and other cognitive abilities that precede dementia. Present treatment of AD mainly focuses on symptomatic slowing the evolution of the disease which is associated with numerous side effects such as dizziness, tiredness, nausea, vomiting, heart attack, and stroke etc. Henceforth; there is urgent need to identify the alternative treatment for management of AD. Herbal medicines have been used from long time to treat AD. One of such leading Phyto molecule is Naringin. It showed promising results against AD but suffers from poor bioavailability and require in high dose to cross the blood brain barrier. Objectives: The main objectives of proposed work are to increase the bioavailability of naringin in brain by developing Nano-suspension and preclinical evaluation of neuroprotective effect of Naringin Nano-suspension (NNS) against Scopolamine induced Alzheimer's disease in rats. Methods: The present study deals with the development, characterization of NNSand to evaluate neuroprotective effect of NNS. Nanoparticles of drug were formed by using PLGA polymer and optimized by using 32 factorial design. Optimized batch was further characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Further the effectiveness of NNS was preclinically investigated by performing AOTstudy as per OECD guideline 420. AD induced Albino Wistar Rats were treated with NNS orally for 14 days and then evaluated for parameters like Gross examination of brain, Relative brain weight determination, behavioural parameters, neuro-inflammatory parameters and immune-histology. Results: Optimization was carried out to study the effect of polymer concentration and number of HPH cycles on Particle size, Poly dispersity index (PDI) and % entrapment efficiency. Desirability search approach was used to select the optimized formulation. Based on the selection criteria, batch F6 having 357.6 ± 05 nm particle size, 0.168 ± 0.04 PDI and 91 ± 2% EE was selected as optimized batch. SEM analysis showed spherical morphology and XRD confirmed the molecular dispersion. Pre-treatment with NNS showed neuroprotective activity basedon results of behavioural studies, biochemical estimation, neuroinflammatory parameters and immunohistochemistry evaluations. Conclusion: As NNS showed significant neuroprotective and anti-neuro-inflammatory effect, this study opens up new ways to exploit Naringin for various therapeutic and restorative purposes.
RESUMEN
Introducción: Etodolac se usa en el tratamiento del dolor agudo y la inflamación. Tiene baja solubilidad debido a la alta hidrofobia y se informa que tras la administración oral muestra alteraciones gástricas. Esto fomenta el desarrollo de formulación tópica en lugar de oral. Método: En este trabajo utilizamos el método de separación de fase de coacervación para el desarrollo del sistema vesicular cargado con etodolaco mediante el uso de tensioactivos no iónicos, colesterol y lecitina de soja. El diseño central compuesto (rotativo) se utilizó para optimizar las concentraciones de lecitina de soja, surfactante y colesterol. Las formulaciones preparadas se caracterizaron por análisis de tamaño de vesículas, potencial zeta, eficiencia de atrapamiento, permeación in vitro, permeación ex vivo y estudio antiinflamatorio. Resultados: Etodolac quedó atrapado con éxito en todas las formulaciones que tenían una eficiencia en el intervalo de 74,36% a 90,85%, siendo mayor a 4 ° C que a temperatura ambiente. Cuando se hidrata con agua, los niosomas se producen espontaneamente el rango de 54 a 141 (por mm cúbico). Los resultados del estudio de difusión in vitro revelaron que el etodolaco se liberó en un rango de 71,86 a 97,16% durante un período de 24 horas. El tamaño medio de vesícula de la formulación optimizada se encontró en 211,9 nm con un PDI de 0,5. Las respuestas observadas, es decir,% de eficacia de encapsulación y liberación de fármaco, fueron 74,12 y 95,08 respectivamente. El potencial zeta fue de -19,4 mV y reveló la estabilidad de la formulación, que fue confirmada adicionalmente por la ausencia de cambios en el contenido del fármaco y la liberación del fármaco después de los estudios de estabilidad. El% de inhibición en el volumen de la pata fue del 40,52% y del 43,61% para la prueba y el gel proniosómico comercializado. (AU)
Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation. Method: In this work we used coacervation-phase separation method for the development of etodolac loaded ve-sicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study. Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel. (AU)
