Márcio Temtem

Green synthesis of a temperature sensitive hydrogel

A thermoresponsive hydrogel, poly(N-isopropylacrylamide), PNIPAAm, with possible applications in drug delivery, tissue engineering and as smart membranes with tuned permeability, was synthesised in supercritical carbon dioxide. A strategy of solvent-free impregnation/coating of polymeric surfaces with PNIPAAm is also suggested, in order to further extend the applications of membranes or porous bulky systems. In this work, in situ synthesis of PNIPAAm within a chitosan scaffold was tested as a proof of concept, in order to produce smart partially-biodegradable scaffolds for tissue engineering applications.

Clean synthesis of molecular recognition polymeric materials with chiral sensing capability using supercritical fluid technology. Application as HPLC stationary phases

Molecularly imprinted polymers (MIPs) of poly(ethylene glycol dimethacrylate) and poly(N-isopropylacrylamide-co-ethylene glycol dimethacrylate) were synthesized for the first time in supercritical carbon dioxide (scCO(2)), using Boc-L-tryptophan as template. Supercritical fluid technology provides a clean and one-step synthetic route for the preparation of affinity polymeric materials with sensing capability for specific molecules. The polymeric materials were tested as stationary HPLC phases for the enantiomeric separation of L- and D-tryptophan. HPLC results prove that the synthesized MIPs are able to recognize the template molecule towards its enantiomer which opens up potential applications in chromatographic chiral separation.

Development of PMMA membranes functionalized with hydroxypropyl-β-cyclodextrins for controlled drug delivery using a supercritical CO2-assisted technology

Cyclodextrin-containing polymers have proved themselves to be useful for controlled release. Herein we describe the preparation of membranes of poly(methylmethacrylate) (PMMA) containing hydroxypropyl-beta-cyclodextrins (HP-beta-CDs) using a supercritical CO(2)-assisted phase inversion method, for potential application as drug delivery devices. Results are reported on the membrane preparation, physical properties, and drug elution profile of a model drug. The polymeric membranes were obtained with HP-beta-CD contents ranging from 0 to 33.4 wt%, by changing the composition of the casting solution, and were further impregnated with ibuprofen using supercritical carbon dioxide (scCO(2)) in batch mode. The influence of the membrane functionalization in the controlled release of ibuprofen was studied by performing in vitro experiments in buffer solution pH at 7.4. The release of the anti-inflammatory drug could be tuned by varying the cyclodextrin content on the membranes.

Development and characterization of a thermoresponsive polysulfone membrane using an environmental friendly technology

A new and environmentally friendly technology has been used successfully to produce thermoresponsive polysulfone membranes with good performance in terms of valve mechanism in the pores, with a complete on-off control of water permeability. Membranes were prepared using a CO2-assisted phase inversion method and their pores were coated/impregnated with a thermoresponsive polymer – poly(N-isopropylacrylamide) – using a new methodology for the preparation of these type of structures. The coating/impregnation efficiency was assessed by SEM and XPS analysis that confirmed the presence of nitrogen due to the thermoresponsive hydrogel. Contact angle measurements and phosphate buffer solution permeability were determined in order to characterize the structure hydrophobicity variations with temperature. The on-off mechanism was tested using a model protein (BSA) as a proof of concept for the ability to control pore apertures by temperature stimulus. A diffusion model based on Ficks law and Langmuir adsorption was developed.

High‐pressure NMR characterization of triacetyl‐β‐cyclodextrin in supercritical carbon dioxide

Cyclodextrins are used in many drug formulations since their cavities provide microenvironments where drug molecules can enter and form inclusion complexes for controlled drug delivery. Supercritical carbon dioxide (scCO2) is an alternative to organic solvents and a very attractive medium for the preparation of these inclusion complexes. The potential ability of triacetyl‐β‐cyclodextrin (TA‐β‐CD) to form inclusion complexes in addition to its high miscibility in liquid and scCO2 could offer a chance for an economical and environmental friendly chemical processing. In this work, high‐pressure NMR studies were performed in order to obtain information on the molecular structure and dynamics of TA‐β‐CD in scCO2 at 313.15 K and 20 MPa and its ability to form inclusion complexes under these conditions was studied. The influence of scCO2 on a number of NMR spectral parameters, such as chemical shifts, spin‐spin coupling constants, nuclear Overhauser effect (NOE) and spin‐lattice relaxation (T1) has been studied. We unequivocally show for the first time structural changes of TA‐β‐CD in scCO2, like acetyl chain orientation and overall shape distortions that can affect its inclusion capability in this medium. The possibility of cavity self‐closure is discussed and the results of two inclusion studies that support cavity self‐closure, with the angiotensin‐converting enzyme inhibitor, captopril, and the nonsteroid anti‐inflammatory drug, flufenamic acid, are presented. Copyright

A visual acoustic high-pressure cell for the study of critical behavior of nonsimple mixtures

A visual acoustic high-pressure cell was constructed for the determination of critical data of multicomponent mixtures. The cell was specially designed to include two piezoelectric transducers and two sapphire windows that make this cell well suited to investigate the critical behavior of mixtures, simultaneously using the acoustic technique and the direct visual inspection of the critical opalescence. Critical data obtained on the binary mixtures of CO2+CHF3 were used for comparison with values given in literature using the traditional methods. The acoustic results are in agreement with those obtained by the conventional methods, within the combined experimental errors. Comparison of visual and acoustic data enabled the evaluation of the applicability of the acoustic technique to study the critical behavior of multicomponent mixtures.

Development of Switchable “Smart” Biomaterials Using an Environmental Friendly Technology

The possibility of using three dimensional porous networks as microreactors for synthesizing thermoresponsive polymers and hydrogels in a CO 2 environment is an important breakthrough in the strategies to prepare smart films, membranes and porous bulky devices that undergo fast reversible changes in surface properties triggered by external stimuli. In situ synthesis of thermoresponsive polymers namely, poly(N-isopropylacrylamide) (PNIPAAm) and poly (N,N-diethylacrylamide) (PDEAAm) within chitosan (CHT), collagen (CLG) and chitosan-collagen (CHT:CLG) blended scaffolds were performed in order to further impregnate with model drugs. The performance of these switchable release devices was evaluated through the study of drug release kinetics as a function of temperature and pH. The same methodology was successfully applied to produce thermoresponsive polysulfone-based membranes.