Publicação
Ionic nanoformulations of neurotherapeutic drugs with enhanced bioavailability
| Resumo: | Alzheimer’s disease (AD) and Parkinson´s disease (PD) are the two most common neurodegenerative diseases. Drug treatments provide control over cognitive and motor manifestations as there is still no cure for these diseases. However, the drugs used to treat these diseases usually exhibit poor brain-blood barrier (BBB) targeting and limited oral bioavailability, which reduces their therapeutic efficacy and increases adverse effects. This work aimed to improve the therapeutic performance of levodopa and tacrine, which are used for PD and AD, respectively, by combining them with various counter-ions to create active pharmaceutical ingredient-based organic salts and ionic liquids (API-OSILs) with higher permeability and solubility. Additionally, the new compounds were added to mesoporous silica nanoparticles (MSNs) to improve the targeting of the API to the BBB, enhancing drug cerebral uptake. To do this, API-OSILs of both drugs were first synthesised and subsequently characterised by spectroscopic (NMR, FTIR), and thermal analysis (DSC). The study of the bioavailability improvement was performed by solubility measurements in water and PBS, as well as octanol/water partition coefficients assays. In all the API-OSILs obtained using levodopa was observed an improvement of solubility. The partition coefficient of all API-OSILs with levodopa and 3 of the 4 API-OSILs synthesised with tacrine suggest an improvement in permeability. Afterward, API-OSILs were bounded covalently to nanoparticles, and then were characterised by DLS (size, polydispersity, zeta potential), UV/Vis, NMR, TGA, XRD, N2 adsorption and elemental analysis (quantification of functionalisation), TEM (morphology) and FTIR (chemical interactions). For MSN functionalised with tacrine a loading of 0.30 mmol/g was obtained, while for the material functionalised with levodopa this value was much lower (0.09 mmol/g). The in vitro API-OSILs release from the MSNs was compared in two mimetic fluids (blood plasma and cerebrospinal fluids) using dialysis bags, being observed a faster and bigger release in mimetic cerebrospinal fluid. |
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| Autores principais: | Gomes, Patrícia do Carmo |
| Assunto: | Levodopa tacrine organic salt and ionic liquid mesoporous silica nanoparticles bioavailability targeting |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Alzheimer’s disease (AD) and Parkinson´s disease (PD) are the two most common neurodegenerative diseases. Drug treatments provide control over cognitive and motor manifestations as there is still no cure for these diseases. However, the drugs used to treat these diseases usually exhibit poor brain-blood barrier (BBB) targeting and limited oral bioavailability, which reduces their therapeutic efficacy and increases adverse effects. This work aimed to improve the therapeutic performance of levodopa and tacrine, which are used for PD and AD, respectively, by combining them with various counter-ions to create active pharmaceutical ingredient-based organic salts and ionic liquids (API-OSILs) with higher permeability and solubility. Additionally, the new compounds were added to mesoporous silica nanoparticles (MSNs) to improve the targeting of the API to the BBB, enhancing drug cerebral uptake. To do this, API-OSILs of both drugs were first synthesised and subsequently characterised by spectroscopic (NMR, FTIR), and thermal analysis (DSC). The study of the bioavailability improvement was performed by solubility measurements in water and PBS, as well as octanol/water partition coefficients assays. In all the API-OSILs obtained using levodopa was observed an improvement of solubility. The partition coefficient of all API-OSILs with levodopa and 3 of the 4 API-OSILs synthesised with tacrine suggest an improvement in permeability. Afterward, API-OSILs were bounded covalently to nanoparticles, and then were characterised by DLS (size, polydispersity, zeta potential), UV/Vis, NMR, TGA, XRD, N2 adsorption and elemental analysis (quantification of functionalisation), TEM (morphology) and FTIR (chemical interactions). For MSN functionalised with tacrine a loading of 0.30 mmol/g was obtained, while for the material functionalised with levodopa this value was much lower (0.09 mmol/g). The in vitro API-OSILs release from the MSNs was compared in two mimetic fluids (blood plasma and cerebrospinal fluids) using dialysis bags, being observed a faster and bigger release in mimetic cerebrospinal fluid. |
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