Nanostructured multilayer compartments : towards multifunctionality and ‘‘cell-like’’ hierarchical complexity

• Autor(a) principal: Costa, Rui R.
• Data de Publicação: 2013
• Outros Autores: Castro, E., Arias, F. J., Rodríguez-Cabello, José Carlos, Mano, J. F.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/22744

In living organisms, there are phenomena that require the presence of specific biomolecules with distinct function and in variable concentra- tions at a given time, such as the healing and regeneration of tissue and organ lesions. In this work, we propose the use of a compartment- ed drug delivery device for the multiple release of bioactive agents. It consists of nanostructured microcapsules confined within a millimetric container that can be easily handled, mimicking the concept of cells which possess organelles with specialized functions. Each hierarchical structure was conceived using the layer-by-layer (LbL) method to form micro and macrocapsules that could individually carry either molecules and release them with distinct kinetics or magnetic nanoparticles (MNPs) to be used in targeted therapies. Furthermore, the internal microcontainers were constructed with a temperature-responsive elas- tin-like recombinamer (ELR) to further add smart properties to the pro- posed system. Sacrificial CaCO3 microparticles empty or entrapping either rhodamine or Fe3O4 MNPs were incubated in chitosan and ELR solutions using LbL for the conception of the microcapsules. Then, the microcapsules were suspended in alginate which was ionically cross- linked in CaCl2 drop-wise. Rhodamine could be encapsulated at this point in the alginate. The bead was coated with chitosan and alginate to build the external macrocapsule compartment. All structures were coated with 3 bilayers. The CaCO3 cores were chelated and the alginate beads liquefied using EDTA. Fluorescence microscopy using FITC and rhodamine markers showed a uniform distribution of the microcap- sules within the macroreservoir. The release of rhodamine from either in the micro or macrocapsule was assessed at 25 and 37 °C in PBS. While the release from the macrocapsule follows a profile similar to that of traditional drug delivery systems, it is more sustained and delayed when released from the internal compartments. Such retention is more pronounced at 37 °C (65% of release in comparison to 90%). This is due to the temperature responsive behavior of ELRs, which undergo a phase transition and make the LbL shell less permeable. For the magnetic response, the incorporation of the MNPs was observed by transmitted light microscopy. The attraction of the devices was observed by applying an external magnetic field along a defined trajec- tory. The results let foresee the use of such multilayer devices as com- partmented structures to encapsulate growth factors, MNPs and stem cells for their controlled differentiation and maintenance or for guided regeneration of tissues and organs.