RESUMO
BACKGROUND: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD). METHODS: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated. RESULTS: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/ß-catenin pathway. The gene expression level of ß-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3ß signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways. CONCLUSION: CNPSGS might be an effective therapeutic alternative for AD treatment.
Assuntos
Alginatos , Doença de Alzheimer , Curcumina , Gelatina , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Impressão Tridimensional , Alicerces Teciduais , Alginatos/química , Gelatina/química , Curcumina/farmacologia , Curcumina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Doença de Alzheimer/tratamento farmacológico , Nanopartículas/química , Alicerces Teciduais/química , Liberação Controlada de Fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/químicaRESUMO
Alzheimer's disease (AD) is a neurodegeneration type that is biologically recognizable via ß-amyloid plaques and tau neurofibril tangles. Global estimation for the total count of individuals enduring AD will rise up to 131 million by 2050. Investigations suggested the existence of a direct proportion between the likelihood of AD occurrence and vitamin B12 (VB12) hypovitaminosis. Approved VB12 administrations, intramuscular and oral, each has serious defects broaching the demand for alternative routes. This work developed VB12-loaded chitosan/tripolyphosphate/polyvinyl alcohol (CS/TPP/PVA) nanoparticles (NPs) embedded in polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone/polycaprolactone (PVP/PCL) nanofibrous (NFs) produced by pressurized gyration (PG) for sublingual and transdermal routes, respectively. Biomaterials were investigated morphologically, chemically, and thermally. Moreover, degradation, disintegration, release behavior, and release kinetics were analyzed. The effectiveness and safety of nanomaterials were assessed and proven with the alamarBlue test on the Aß1-42-induced SH-SY5Y model. The final evaluation suggested the feasibility, safety, and effectiveness of produced systems. Consequently, two alternative VB12 application routes were developed with high effectivity and low toxicity with the power of nanotechnology.
