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Ionic Nanoformulations of Neurothera...

do Carmo Gomes, Patricia,

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Ionic Nanoformulations of Neurotherapeutic Drugs with Enhanced Bioavailability /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Ionic Nanoformulations of Neurotherapeutic Drugs with Enhanced Bioavailability // Patricia do Carmo Gomes.
Author:	do Carmo Gomes, Patricia,
Description:	1 electronic resource (197 pages)
Notes:	Source: Masters Abstracts International, Volume: 86-05.
Contained By:	Masters Abstracts International86-05.
Subject:	Alzheimer's disease. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31745923
ISBN:	9798346732167

Ionic Nanoformulations of Neurotherapeutic Drugs with Enhanced Bioavailability /
do Carmo Gomes, Patricia,

Ionic Nanoformulations of Neurotherapeutic Drugs with Enhanced Bioavailability /Patricia do Carmo Gomes. - 1 electronic resource (197 pages)

Source: Masters Abstracts International, Volume: 86-05.

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.

English

ISBN: 9798346732167Subjects--Topical Terms:

588010
Alzheimer's disease.

Ionic Nanoformulations of Neurotherapeutic Drugs with Enhanced Bioavailability /
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100 1 $a do Carmo Gomes, Patricia, $e author. $3 3828327
245 1 0 $a Ionic Nanoformulations of Neurotherapeutic Drugs with Enhanced Bioavailability / $c Patricia do Carmo Gomes.
264 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 1 electronic resource (197 pages)
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500 $a Source: Masters Abstracts International, Volume: 86-05.
500 $a Advisors: Gago, Sandra; Petrovski, Zeljko Committee members: de Sousa, Joao Aires; Ventura, Marcia; Gago, Sandra.
502 $b M.S. $c Universidade NOVA de Lisboa (Portugal) $d 2023.
520 $a 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.
520 $a A doenca de Alzheimer (DA) e a doenca de Parkinson (DP) sao as duas doencas neurodegenerativas mais comuns. Os medicamentos existentes permitem controlar os sintomas cognitivos e motores, uma vez que ainda nao existe cura para estas doencas. No entanto, os farmacos utilizados para tratar estas doencas apresentam geralmente um fraco direcionamento para a barreira hematoencefalica (BBB) e uma biodisponibilidade oral limitada, o que reduz a sua eficacia terapeutica e aumenta os efeitos adversos.Este trabalho teve como objetivo melhorar o desempenho terapeutico da levodopa e da tacrina, que sao usadas para a PD e AD, respetivamente, combinando-as com varios contra-ioes para criar sais organicos e liquidos ionicos baseados em ingredientes farmaceuticos ativos (API-OSILs) com maior permeabilidade e solubilidade. Alem disso, os novos compostos foram adicionados a nanoparticulas de silica mesoporosa (MSNs) para melhorar o direcionamento do API para a BBB, aumentando a captura do medicamento no cerebro.Para tal, os API-OSIL de ambos os farmacos foram primeiramente sintetizados e de seguida foram caracterizados por analise espectroscopica (NMR, FTIR) e termica (DSC). O estudo da melhoria da biodisponibilidade foi efetuado por medicoes de solubilidade em agua e PBS, bem como por ensaios de coeficientes de particao octanol/agua. Em todos os API-OSILs obtidos com levodopa foi observada uma melhoria da solubilidade. Os coeficientes de particao de todos os API-OSILs com levodopa e de 3 dos 4 API-OSILs sintetizados com tacrina sugerem uma melhoria da permeabilidade.Posteriormente, os API-OSILs foram ligados covalentemente a nanoparticula, sendo depois caracterizados por DLS (tamanho, polidispersidade, potencial zeta), UV/Vis, NMR, TGA, XRD, adsorcao de N2 e analise elementar (quantificacao da funcionalizacao), TEM (morfologia) e FTIR (interacoes quimicas). Para o MSN funcionalizado com tacrina foi obtido uma funcionalizacao de 0,30 mmol/g, enquanto para o material funcionalizado com levodopa este valor foi muito inferior (0,09 mmol/g).A libertacao in vitrode API-OSILs das MSNs foi comparada em dois fluidos mimeticos (plasma sanguineo e cerebrospinal) utilizando sacos de dialise, tendo sido observada uma libertacao mais rapida e maior no fluido mimetico cerebrospinal.
546 $a English
590 $a School code: 7029
650 4 $a Alzheimer's disease. $3 588010
650 4 $a Spectrum analysis. $3 520440
650 4 $a Pharmaceuticals. $3 3562593
650 4 $a Parkinson's disease. $3 844182
650 4 $a Analytical chemistry. $3 3168300
650 4 $a Neurosciences. $3 588700
650 4 $a Optics. $3 517925
650 4 $a Pharmaceutical sciences. $3 3173021
690 $a 0486
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710 2 $a Universidade NOVA de Lisboa (Portugal). $e degree granting institution. $3 3767537
720 1 $a Gago, Sandra $e degree supervisor.
720 1 $a Petrovski, Zeljko $e degree supervisor.
773 0 $t Masters Abstracts International $g 86-05.
790 $a 7029
791 $a M.S.
792 $a 2023
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31745923