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Projeto de investigação
Smart porous particles for pulmonary drug and vaccine delivery
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Publicações
Multifunctional nano-in-micro formulations for lung cancer theragnosis
Publication . Silva, Ana Sofia Matias da; Aguiar-Ricardo, Ana; Correia, Ilídio
Polyurea dendrimer for efficient cytosolic siRNA delivery
Publication . Restani, Rita B.; Conde, João; Baptista, Pedro V.; Cidade, Maria Teresa; Bragança, Ana M.; Morgado, Jorge; Correia, Ilídio J.; Aguiar-Ricardo, Ana; Bonifácio, Vasco D. B.; DQ - Departamento de Química; LAQV@REQUIMTE; DCV - Departamento de Ciências da Vida; Centro de Investigação em Genética Molecular Humana (CIGMH); CENIMAT-i3N - Centro de Investigação de Materiais (Lab. Associado I3N); DCM - Departamento de Ciência dos Materiais; RSC - Royal Society of Chemistry
The design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are 'smart' biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.
Dry powder formulations containing bioactive compounds from marine Actinobacteria
Publication . Almeida, Vanessa Clemente; Aguiar-Ricardo, Ana
Lower respiratory infections were the leading cause of sickness and mortality in 2013.1 The treatment of such infections relies on antibiotic therapy. However, antibiotic resistance to human pathogens and the prevalence of new cancer types continues to increase, so it is imperative not only to discover new lead-like drugs agents, but also develop new drug delivery systems for pulmonary diseases.2,3 In order to achieve such goal, it was isolated and elucidated antibacterial compounds from a marine-sediment-derived Actinobacteria, collected along Madeira archipelago. These bioactive compounds were obtained from Streptomyces aculeolatus, PTM-029, belonging to the MAR4 group. The structures of these compounds were elucidated by 1D and 2D NMR, HR-MS and other spectroscopic data. The antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium EF82 (VRE) were determined for the most promising compound isolated from PTM-029, with a minimum inhibitory concentration (MIC) of 1,95 μg/mL for both bacterial pathogens. Subsequently, chitosan and cholesterol-based dry powder formulations were manufactured, containing encapsulated POxylated polymer, efficiently synthesized using a supercritical-assisted polymerization in carbon dioxide (CO2), end-capped to a model drug ibuprofen (IBP) and a marine bioactive compound, PTM-029, F4, F39. The dry powder formulations (DPF) were then synthesized through the Supercritical Assisted Spray-Drying (SASD) technique. All the produced DPFs were characterized in detail in relation to their morphology, physical-chemical properties and aerodynamic performance. The resulting particles showed good aerodynamic diameters between the 1 and 7 μm, yields up to 45% and FPF percentages rounding the 71%, as well as the required morphology to make them suitable for pulmonary delivery.
Polyurea-based dendrimer therapeutics
Publication . Silva, Ana Rita Bernardo Restani da; Aguiar-Ricardo, Ana
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
3599-PPCDT
Número da atribuição
PTDC/EQU-EQU/116097/2009