Publicação
Development of quercetin-loaded liposomal dry powder formulations for the treatment of inflammatory lung diseases
| Resumo: | Quercetin, the main flavonoid found in vegetables and fruits has been described to have wide range of health benefits with antioxidant/anti-inflammatory properties. Due to its low aqueous solubility and low bioavailability, this natural compound requires a drug delivery system. Liposomes, which are concentric lamellar vesicles mainly composed of phospholipids are well-known nanocarriers for drug delivery with non-toxic characteristics and biocompatible with cells, are very attractive for transporting quercetin. However, to be efficiently inhalable, an excipient that confers aerodynamic characteristics is necessary. Therefore, the objective of this thesis is to convert quercetin encapsulated in liposomes into quercetin-loaded liposomal dry powder formulations for the treatment of inflammatory lung diseases using a sustainable process – supercritical CO2 - assisted spray drying (SASD). In this way, liposomes were firstly prepared with different surface electric charges (neutral, positive, negative) varying the lipid-to-quercetin molar ratios (10:0.5, 10:1 and 10:1.5). Moreover, PEGylated liposomes were produced due to their well described prolonged time in blood circulation and their ability to significantly improve the delivery of drugs to the desired target. Herein, it was possible to prepare non-PEGylated positive charge formulations (10:0.5 (mol:mol) quercetin-to-lipid ratio) with 92 % lipid yield and 99 % incorporation efficiency. Next, the best formulations were selected considering the incorporation efficiency of quercetin, the size and polydispersion index of liposomes and the lipid yield, for further processing in the SASD. The non-PEGylated liposomal formulations with a positive superficial charge (10:0.5 mol:mol) were atomized using as excipient trehalose and leucine, producing nano-in-microparticles with an average diameter of 5.91 μm and a water content of 5 %. Physicochemical characterization suggested that liposomes are encapsulated in the powder. Further aerodynamic studies have shown that non-PEGylated positive charge formulations (10:0.5 mol:mol) of dry powders are suitable for inhalation because they have a fine particle fraction of 46 % and an average aerodynamic diameter of 1.37 μm. The powders produced by SASD, after the rehydration of excipients and resuspension of liposomes, were characterized to verify the incorporation efficiency of quercetin, as well as the size and polydispersion of liposomes. It was concluded that the resuspended liposomes presented an average size of 208 nm, with a lipid yield of 30 % and an incorporation efficiency of quercetin of 42 % (non-PEGylated liposomal formulation made with a positive charge lipid 10:0.5 mol:mol) having better incorporation efficiency results. |
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| Autores principais: | Casaca, Ana Sofia Brito |
| Assunto: | Quercetin Liposomes Supercritical CO2- assisted spray drying |
| Ano: | 2022 |
| 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: | Quercetin, the main flavonoid found in vegetables and fruits has been described to have wide range of health benefits with antioxidant/anti-inflammatory properties. Due to its low aqueous solubility and low bioavailability, this natural compound requires a drug delivery system. Liposomes, which are concentric lamellar vesicles mainly composed of phospholipids are well-known nanocarriers for drug delivery with non-toxic characteristics and biocompatible with cells, are very attractive for transporting quercetin. However, to be efficiently inhalable, an excipient that confers aerodynamic characteristics is necessary. Therefore, the objective of this thesis is to convert quercetin encapsulated in liposomes into quercetin-loaded liposomal dry powder formulations for the treatment of inflammatory lung diseases using a sustainable process – supercritical CO2 - assisted spray drying (SASD). In this way, liposomes were firstly prepared with different surface electric charges (neutral, positive, negative) varying the lipid-to-quercetin molar ratios (10:0.5, 10:1 and 10:1.5). Moreover, PEGylated liposomes were produced due to their well described prolonged time in blood circulation and their ability to significantly improve the delivery of drugs to the desired target. Herein, it was possible to prepare non-PEGylated positive charge formulations (10:0.5 (mol:mol) quercetin-to-lipid ratio) with 92 % lipid yield and 99 % incorporation efficiency. Next, the best formulations were selected considering the incorporation efficiency of quercetin, the size and polydispersion index of liposomes and the lipid yield, for further processing in the SASD. The non-PEGylated liposomal formulations with a positive superficial charge (10:0.5 mol:mol) were atomized using as excipient trehalose and leucine, producing nano-in-microparticles with an average diameter of 5.91 μm and a water content of 5 %. Physicochemical characterization suggested that liposomes are encapsulated in the powder. Further aerodynamic studies have shown that non-PEGylated positive charge formulations (10:0.5 mol:mol) of dry powders are suitable for inhalation because they have a fine particle fraction of 46 % and an average aerodynamic diameter of 1.37 μm. The powders produced by SASD, after the rehydration of excipients and resuspension of liposomes, were characterized to verify the incorporation efficiency of quercetin, as well as the size and polydispersion of liposomes. It was concluded that the resuspended liposomes presented an average size of 208 nm, with a lipid yield of 30 % and an incorporation efficiency of quercetin of 42 % (non-PEGylated liposomal formulation made with a positive charge lipid 10:0.5 mol:mol) having better incorporation efficiency results. |
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