Publicação
Integrated manufacture of Liposomal dry powder formulations
| Resumo: | Chronic respiratory diseases (CRDs) affect the airways and other structures of the lungs. CRDs are not curable, and it is estimated by the World Health Organization, 70 % of deaths under 70 years of age occur in low- and middle-income countries. Anti-inflammatory-based therapies may result in several adverse side effects. To address this problem, a synergy between pharmaceutical and supercritical carbon dioxide techniques is established for the manufacturing of inhaled enzyme and natural products-based anti-inflammatory therapies. In this work, enzyme (SOD)/quercetin (Quer) - loaded liposomal formulations were converted into liposomal dry powder formulations (Lip-DPFs) for the treatment of inflammatory lung diseases, using supercritical CO2-assisted spray-drying (SASD). First, liposomal formulations were produced using distinct methods - microfluidics and thin-film method hydration. Microfluidics showed to be able to encapsulate both low and high molecular weight proteins, while pre-serving the conformational structure and enzyme activity. Secondly, a quality-by-design approach was applied towards the Lip-DPFs optimization using a low molecular weight hydrophilic dye as a model molecule. Stability studies proved that powders remain stable for 30 days at a relative humidity of 4 %. Translating the knowledge, the optimized parameters and formulations were applied to the production of SOD-loaded liposomal dry powder formulations (SOD_Lip-DPFs) for inhalation. Resuspended SOD-loaded liposomes showed structural maintenance and enzyme protection, regarding the SOD encapsulation efficiency and enzyme activity retention. SOD_Lip-DPFs showed to be able to inhalation, reaching the respiratory region, namely terminal bronchi. Finally, hydrophobic molecule-loaded liposomal dry powder formulations (Quer_Lip-DPFs) were produced with suitable aerodynamic properties. Overall, the work herein detailed represents an innovative, robust, upscaling, and time-efficient technique for drying liposomes, keeping them stable during storage and overcoming the common drawbacks of current drying and storage methods. |
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| Autores principais: | Sequeira, Clarinda Isabel da Silva e Costa |
| Assunto: | Biopharmaceuticals flavonoids liposomes solid dosage forms pulmonary delivery supercritical CO2-assisted spray-drying |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Chronic respiratory diseases (CRDs) affect the airways and other structures of the lungs. CRDs are not curable, and it is estimated by the World Health Organization, 70 % of deaths under 70 years of age occur in low- and middle-income countries. Anti-inflammatory-based therapies may result in several adverse side effects. To address this problem, a synergy between pharmaceutical and supercritical carbon dioxide techniques is established for the manufacturing of inhaled enzyme and natural products-based anti-inflammatory therapies. In this work, enzyme (SOD)/quercetin (Quer) - loaded liposomal formulations were converted into liposomal dry powder formulations (Lip-DPFs) for the treatment of inflammatory lung diseases, using supercritical CO2-assisted spray-drying (SASD). First, liposomal formulations were produced using distinct methods - microfluidics and thin-film method hydration. Microfluidics showed to be able to encapsulate both low and high molecular weight proteins, while pre-serving the conformational structure and enzyme activity. Secondly, a quality-by-design approach was applied towards the Lip-DPFs optimization using a low molecular weight hydrophilic dye as a model molecule. Stability studies proved that powders remain stable for 30 days at a relative humidity of 4 %. Translating the knowledge, the optimized parameters and formulations were applied to the production of SOD-loaded liposomal dry powder formulations (SOD_Lip-DPFs) for inhalation. Resuspended SOD-loaded liposomes showed structural maintenance and enzyme protection, regarding the SOD encapsulation efficiency and enzyme activity retention. SOD_Lip-DPFs showed to be able to inhalation, reaching the respiratory region, namely terminal bronchi. Finally, hydrophobic molecule-loaded liposomal dry powder formulations (Quer_Lip-DPFs) were produced with suitable aerodynamic properties. Overall, the work herein detailed represents an innovative, robust, upscaling, and time-efficient technique for drying liposomes, keeping them stable during storage and overcoming the common drawbacks of current drying and storage methods. |
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