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Ethaline as a Putative Drug Delivery System for Niraparib
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Resumo(s)
The poor solubility of Active Pharmaceutical Ingredients (APIs) is one of the biggest challenges
faced by the pharmaceutical industry. A major focus recently has not been so much on the development
of new APIs but the enhancement of the pharmacokinectic properties of already existing ones. Deep
Eutectic Solvents (DES) are a class of relatively new solvents, characterized by being a mixture of two
or more components that, when mixed together, suffer a major depression of the melting point, relative
to the individual components. The DES used in this work is ethaline, a mixture of choline chloride and
ethylene glycol in a 1:2 ratio. Niraparib is an API used originally to treat breast cancer although it has
also been studied to treat other forms of cancer.
This work comprises of an experimental component, involving solubility determinations, pH assays,
and water/DES fractions studies; and a computational component that included the study of the solvent’s
structure, encompassing the role of water, and the API’s solvation free energy (DGsolv).
The results show an increase of about a decade of the solubility in the DES compared to water and
PBS. The DES led to a basification of the medium in PBS. More detailed studies showed that both
components of the DES lead to a pH increase.
The simulation studiesrevealed that the API is heavily solvated by the DES even at low DES contents
in aqueous solutions. The free energy studies showed that the major factor responsible for the solubility
enhancement is the enthalpic contribution. This means that the solubility increase is almost exclusively
related to the API-solvent interactions.
Future studies, should involve, the development of a therapeutic DES (THEDES) using Niraparib as
a DES component, API-DES encapsulation, as well as the assessment of the potential of this (or other)
DES to modulate the pH of the cancer acidic microenvironment.
Descrição
Tese de mestrado, Química (Química), 2024, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Cancro Solventes Eutécticos Profundos (DES) Solubilidade Energia Livre de Solvatação Sistema de Administração de Fármacos Teses de mestrado - 2024