Novel approach over template molecule elimination in molecularly imprinted polymers by using heat activated persulfate.

This study proposes a new alternative for template removal from molecularly imprinted polymers by heat activated persulfate. It is known that trace amounts of template molecule remains in the polymer network after extraction by current methodologies leading to bleeding and incomplete removal of template which could compromise final determination of target analytes especially in trace analysis. A previously developed molecularly imprinted polymer specially designed for Coenzyme Q10 (CoQ10) extraction was employed as a model to test this template elimination approach. This polymer is based on methacrylic acid and ethylene glycol dimethylacrylate as monomers and Coenzyme Q0 as template. This coenzyme has the same quinone group as the CoQ10. Selectivity was analyzed comparing the recovery of CoQ10 and ubichromenol, a CoQ10 related substance. Chemical degradation using heat-activated persulfate allows the elimination of the template molecule with a high level of efficiency, being a simple and ecological methodology, yielding a polymer that exhibits comparable selectivity and imprinting effect with respect to traditional extraction methods.

Development and in vitro evaluation of potential electromodulated transdermal drug delivery systems based on carbon nanotube buckypapers.

Buckypapers based on different types of carbon nanotubes with and without the addition of four model drugs, two of basic nature (clonidine hydrochloride, selegiline hydrochloride) and the others of acidic character (flurbiprofen, ketorolac tromethamine) were prepared and characterized. The influence of the conditions employed in the preparation of the buckypapers (dispersion time and solvents used in the preparation, as well as the type of carbon nanotubes used and the characteristics of the drug involved) on their conductivity was especially examined. The in vitro performance of the drug loaded buckypapers as passive and active transdermal drug release systems, the latter being modulated by means of the application of electric voltages, was studied. Passive drug loaded buckypapers presented characteristic release profiles, also depending on the drug used, which indicate differences in the drug-carbon nanotubes non-covalent interactions. Application of electrical biases of appropriate polarities enabled the modulation of the drug release profiles in any desired direction. Different mathematical models were fitted to passive and electromodulated experimental release data for the four model drugs. Among these models, the most appropriate for data description was a two-compartment pseudo-second-order one.

Carbon nanotubes buckypapers for potential transdermal drug delivery.

Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT-drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect.

Cationization of kappa- and iota-carrageenan--Characterization and properties of amphoteric polysaccharides.

Commercial kappa- and iota carrageenans were cationized with 3-chloro-2-hydroxypropyltrimethylammonium chloride in aqueous sodium hydroxide solution. For kappa-carrageenan three derivatives with different degrees of substitution were obtained. Native and amphoteric kappa-carrageenans were characterized by NMR and infrared spectroscopy, scanning electron and atomic force microscopy; methanolysis products were studied by electrospray ionization mass spectrometry. Young moduli and the strain at break of films, differential scanning calorimetry, rheological and flocculation behavior were also evaluated; the native and the amphoteric derivatives showed different and interesting properties. Cationization of iota-carrageenan was more difficult, indicating as it was previously observed for agarose, that substitution starts preferentially on the 2-position of 3,6-anhydrogalactose residues; in iota-carrageenan this latter unit is sulfated.

Preparation and characterization of controlled release matrices based on novel seaweed interpolyelectrolyte complexes.

Novel interpolyelectrolyte complexes (IPECs) between naturally sulfated polysaccharides of the seaweed Polysiphonia nigrescens (PN) and cationized agaroses (CAG) and Eudragit E (EE) were prepared using an organic solvent free process, characterized, and explored for controlled drug release. Tablets containing model drug ibuprofen and IPECs were prepared by direct compression. Drug release in acid medium was low owing to the low solubility of ibuprofen in that condition and to the matrix action. Zero order drug release was determined in the buffer stage (pH=6.8), with Fickian diffusion predominating over relaxation during the initial phases. Relaxation appears to increase along the release process and even overcomes diffusion for some systems. Drug release profiles could be controlled by varying the content of IPECs in the tablets. Also, the change in molecular weight and the degree of substitution of the components allowed altering the release profiles.

Studies on the cationization of agarose.

Cationized agaroses with different degrees of substitution (0.04-0.77) were synthesized, employing 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC). The influence of different reaction parameters on the substitution degree and molecular weight was evaluated. The investigated parameters were concentration of reagents, temperature, time, and addition of NaBH(4). The products were characterized by means of scanning electronic microscopy, infrared spectroscopy, viscosimetry, and NMR spectroscopy. Methanolysis products were studied by electrospray ionization mass spectrometry. The higher the concentration of CHPTAC employed, a higher degree of substitution was obtained, if the optimum concentration of NaOH in each case was employed. Insufficient quantities of NaOH reduced epoxide formation and the reacting alkoxides of the polysaccharide, whereas an excess of NaOH favored degradation of the epoxide and decrease in the molecular weight of the product. A reaction time of 2h was sufficient to obtain products with the maximum degree of substitution for each case. The addition of NaBH(4) gave products with a slightly higher molecular weight, but the extra cost involved should not justify its use for large-scale application.

Preparation and characterization of a novel starch-based interpolyelectrolyte complex as matrix for controlled drug release.

A novel cationized starch-based interpolyelectrolyte complex (IPEC) was formed using kappa-carrageenan as the counter polyion. Characterization of the product by turbidity measurements and elemental analyses indicated a 1:1 interaction of the repeating units. FT-IR spectra for the IPEC showed some differences in comparison with either IPEC constituents or physical mixture. The swelling of tablets obtained by direct compression was independent of pH, and a maximum value of 742% was attained after 24h. The performance of the IPEC as matrix for controlled release of ibuprofen indicates that drug delivery takes place in a zero-order manner. Experimental dissolution data in the buffer stage were properly represented by a model accounting for contributions of Fickian diffusion and relaxation phenomena; this model suggests that the former predominates over the latter, for the modeled range.