Development of multifunctional composite aerosols for lung cancer therapy

• Autor(a) principal: Silva, Marta Chaves
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/74795
• topic: lung cancer; dry powders; supercritical carbon dioxide; nanoparticles; microparticles; supercritical assisted spray-drying; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Lung cancer is the most common type of cancer worldwide with an exponential growth every year. Besides the lately diagnose, lung cancer treatments are often limited to chemother-apy and radiotherapy, both presenting devastating side effects for the patient. Therefore there is a need of developing new ways to fight this problem. Nanotechnology and pulmonary delivery have been combined in order to develop pulmonary drug delivery systems that are able to reach the deep lung and release a drug into lung cancer cells. Herein we present a new strategy based on the synthesis of strawberry-like gold-coated magnetic nanoparticles (Fe@Au NPs) that are later conjugated with micronization technologies in order to produce respirable dry powders, nano-in-micro formulations. Once surface modifica-tions can be easily made by coating the nanoparticle with a fluorescent polymer, the functionali-zation of these Fe@Au NPs in aqueous media is proposed using a fluorescent oligomer oligo(2-ethyl-2-oxazoline) endcapped with cysteamine. Fe@Au nanoparticles functionalized with this new class of oligomers (OOxs), synthetized in supercritical carbon dioxide (scCO2), were mi-cronized into polymeric powders in order to produce respirable powders that are able to reach the deep lungs. Once in the lung epithelia, the chosen biodegradable and biocompatible carrier, chitosan (CHT) is expected to release the nanoformulations in a controlled and sustained man-ner. The micronization process was achieved using sustainable methodologies that also make use of scCO2, the Supercritical Assisted Spray Drying (SASD). The co-atomization of a casting solution with CHT and the produced nanoparticles enabled the production of dry powders with suitable features for pulmonary delivery. The ability of the engineered nanosystems to degrade and release its encapsulated contents was addressed by co-encapsulating the nanoparticles with a model drug (ibuprofen). The optimal conditions for the production of the dry powders were carefully selected by performing a design of experiment (DoE). With the best conditions chosen, two assays were made, one containing the nanoparticles and CHT, and the other con-taining the nanoparticles, ibuprofen and CHT. Aerodynamic, morphological and physical-chemical characterizations were assessed. Nanoparticles with diameters ranging from 50-200 nm and microparticles with diameters of approximately 3 μm were obtained. The produced dry powders showed great aerodynamic properties, with fine particle fraction values around 60% and mass median aerodynamic diameters around 1.5 μm. An 80% of drug release was achieved after 48 hours of study. These preliminary results show that these nano-in-micro for-mulations could be potential systems to address pulmonary administration of magnetic nanopar-ticles.