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The impact of liquid lipid in the formulation for topical ocular application of lipid-polymer hybrid nanoparticles: drug loading and release profile
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Resumo(s)
"As principais estratégias para melhorar a biodisponibilidade ocular de
fármacos incluem o uso de potenciadores de solubilidade e de penetração incorporados
na formulação, visando facilitar a passagem pela córnea. Este estudo tem como objetivo
aperfeiçoar tratamentos tópicos ao aumentar a biodisponibilidade do fármaco, através da
incorporação de lípido líquido em nanopartículas híbridas lípido-polímero para
melhorar a liberação controlada do fármaco.
As nanopartículas lipídicas de nanoestrutura híbrida (HyNLCs), produzidas de
acordo com a metodologia previamente publicada pelo nosso grupo, foram
desenvolvidas com base em estudos de solubilidade de dois fármacos modelo,
Ibuprofeno/Levofloxacina. As HyNLCs foram caracterizadas quanto ao tamanho (200-
400 nm), índice de polidispersidade (PdI) (0.300-0.500) e Potencial Zeta (ζP) (-40 a +
13). A eficiência de encapsulação (%EE) foi de 94.3 ± 1.4%, 100.0 ± 0.7% e 90.2 ±
2.9%, enquanto a carga de fármaco (%DL) foi de 2.04 ± 0.04%, 40.0 ± 0.3% e 4.52 ±
0.14% para o antibiótico, anti-inflamatório, e co-encapsulação, respetivamente. A
análise por Calorimetria Diferencial de Varrimento (DSC) revelou que os fármacos
encapsulados assumiram uma forma amorfa, sugerindo um possível aumento na
biodisponibilidade. Além disso, a análise por FTIR-ATR indicou a presença dos
mesmos nas nanopartículas. Os ensaios de libertação demonstraram que as HyNLCs
aumentaram em 20% a quantidade cumulativa de fármaco libertado, em comparação
com as nanopartículas lipídicas sólidas híbridas (HySLNs). Portanto, a presença do
lípido líquido contribui para a biodisponibilidade do fármaco sem prejudicar o sistema
de libertação.
As HyNLCs foram testadas in vitro na linha celular ARPE-19, mantendo a
integridade membranar e atividade metabólica, com viabilidade celular superior a 90%.
Resumindo, este estudo conduziu à criação de HyNLCs biocompatíveis, com
propriedades mucoadesivas e uma libertação eficiente de fármaco, contribuindo para a
absorção do farmáco e aumento significativo da sua biodisponibilidade.
The main strategies that can be used to improve the ocular drug bioavailability include the use of solubility enhancers and drug penetration enhancers that can be incorporated into the formulation to assist their transit across the cornea. The present work is intended to satisfy the need to improve the topical treatments by increasing the drug bioavailability. Thus, the incorporation of a liquid lipid in lipid-polymer hybrid nanoparticles will improve the controlled release of the drug. The hybrid nanostructure lipid carriers (HyNLCs) were produced according to a published methodology of our research group. The incorporation of liquid lipid into HyNLCs was selected based on solubility studies of two model drugs Ibuprofen /Levofloxacin. HyNLCs were characterized in terms of size (200-400 nm), polydispersity index (PdI), (0.300-0.500) and zeta potential (P) (-40 to + 13 mV). The encapsulation efficiency (%EE), were 94.3 1.4%, 100.0 0.7% and 90.2 2.9% the drug loading (%DL) of 2.04 0.04%, 40.0 0.3% and 4.52 0.14% for the antibiotic, anti-inflammatory and co-encapsulation, respectively. Differential Scanning Calorimetry (DSC) analysis revealed that the encapsulated drugs assumed an amorphous form, suggesting a potential enhancement in bioavailability. Furthermore, FTIR-ATR analysis indicated the presence of the drugs within the nanoparticles. The release assay showed that HyNLCs in comparison with hybrid solid lipid nanoparticles (HySLNs) had an increase of 20% of cumulative amount of drug release. Thus, the presence of the liquid lipid contributes to the bioavailability of the drug without compromising the properties of delivery system. The HyNLCs were in vitro uptake by ARPE-19 cell line without comprising its membrane integrity and metabolic activity with >90% of cell viability. In summary, this research has resulted in the development of biocompatible HyNLCs with mucoadhesive properties and improved drug release, contributing to enhance drug absorption and increase overall bioavailability.
The main strategies that can be used to improve the ocular drug bioavailability include the use of solubility enhancers and drug penetration enhancers that can be incorporated into the formulation to assist their transit across the cornea. The present work is intended to satisfy the need to improve the topical treatments by increasing the drug bioavailability. Thus, the incorporation of a liquid lipid in lipid-polymer hybrid nanoparticles will improve the controlled release of the drug. The hybrid nanostructure lipid carriers (HyNLCs) were produced according to a published methodology of our research group. The incorporation of liquid lipid into HyNLCs was selected based on solubility studies of two model drugs Ibuprofen /Levofloxacin. HyNLCs were characterized in terms of size (200-400 nm), polydispersity index (PdI), (0.300-0.500) and zeta potential (P) (-40 to + 13 mV). The encapsulation efficiency (%EE), were 94.3 1.4%, 100.0 0.7% and 90.2 2.9% the drug loading (%DL) of 2.04 0.04%, 40.0 0.3% and 4.52 0.14% for the antibiotic, anti-inflammatory and co-encapsulation, respectively. Differential Scanning Calorimetry (DSC) analysis revealed that the encapsulated drugs assumed an amorphous form, suggesting a potential enhancement in bioavailability. Furthermore, FTIR-ATR analysis indicated the presence of the drugs within the nanoparticles. The release assay showed that HyNLCs in comparison with hybrid solid lipid nanoparticles (HySLNs) had an increase of 20% of cumulative amount of drug release. Thus, the presence of the liquid lipid contributes to the bioavailability of the drug without compromising the properties of delivery system. The HyNLCs were in vitro uptake by ARPE-19 cell line without comprising its membrane integrity and metabolic activity with >90% of cell viability. In summary, this research has resulted in the development of biocompatible HyNLCs with mucoadhesive properties and improved drug release, contributing to enhance drug absorption and increase overall bioavailability.
Descrição
Tese de mestrado, Ciências Biofarmacêuticas , 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
HyNLCs Lipids Nanoparticles Topical Ocular Teses de mestrado - 2023