Irina Popescu

Phosphorylated curdlan microgels. Preparation, characterization, and in vitro drug release studies.

Curdlan derivative with anionic phosphate groups was used for the first time to obtain hydrogel microspheres. The chemical cross-linking of the phosphorylated curdlan was performed with epichlorohydrin using the water-in-oil inverse emulsion technique. The optical and scanning electron microscopies were used to analyze the morphology of the microgels, whereas the FTIR spectroscopy was used to investigate their chemical structure. The main characteristics such as the swelling degree, the exchange capacity, and the thermal resistance were also studied. These new anionic microgels could be used as potential carriers for controlled release of opposite charged drugs retained through electrostatic forces. Diphenhydramine, a cationic model drug, was used to investigate the loading and the release processes in various pH media simulating physiological fluids. Several mathematical models were applied to evaluate the drug transport processes and to calculate the drug diffusion coefficients. The synthesized microspheres presented an excellent biocompatibility.

Cationic curdlan: Synthesis, characterization and application of quaternary ammonium salts of curdlan.

Water-soluble curdlan derivatives containing quaternary ammonium groups with a degree of substitution up to 0.15 were synthesized using different cationic agents in alkaline medium. The chemical structure of curdlan derivatives was confirmed by FTIR, (13)C and (1)H NMR spectroscopy. The influence of some reaction conditions (temperature, time, and molar ratio) on the degree of substitution and the viscosimetic behaviour were studied. The degree of substitution increased with the amount of the cationization agent per anhydroglucose unit and was higher when the glycidyl reagents were used, compared with the case when the reagents contained chloro-hydroxypropyl groups. The viscosity behaviour of these new derivatives of curdlan in aqueous solutions and the values of intrinsic viscosities calculated using different semi-empirical equations denote a high hydrodynamic dimension of the macromolecular coils. The interaction of these cationic curdlan derivatives with an anionic curdlan (monobasic curdlan phosphate) was studied in situ by turbidimetric measurements and after 24h by optical density and dynamic light scattering. The formation of polyelectrolyte complexes was influenced by the degree of substitution, the nature of the quaternary substituent, and by the ionic strength of the aqueous solution. The morphology of the polyelectrolyte complexes particles in dry state was examined by atomic force microscopy.

Synthesis and Investigation of Double Stimuli-Responsive Behavior of N-Isopropylacrylamide and Maleic Acid Copolymer in Solutions

Poly(N-isopropylacrylamide-co-maleic acid) [poly(NIPAAm-co-MA)] linear copolymer with comonomer molar ratio NIPAAm:MA = 94:6 was synthesized by free-radical copolymerization. The molar mass, MsD = 28,000 Da, of poly(NIPAAm-co-MA) was determined using hydrodynamic methods. The self-assembly of poly(NIPAAm-co-MA) in aqueous solution at a concentration of 0.015 g cm−3 within the pH interval from 1.8 to 10.6 and the temperature interval from 22 to 60°C was investigated by static and dynamic light scattering. The copolymer showed a double temperature and pH responsiveness. Three types of particles, namely, macromolecules (or unimers), micellar-like structures, and loose aggregates existed in the poly(NIPAAm-co-MA) aqueous solutions. The fraction of dissolved entities and the hydrodynamic radii of the micellar-like structures and loose aggregates depended considerably on temperature and pH. The temperature of the phase separation and the width of the phase separation interval increased with pH. An influence of pH on kinetic processes in poly(NIPAAm-co-MA) solutions was observed.

Thermo- and pH-sensitivity of poly(N-vinylcaprolactam-co-maleic acid) in aqueous solution

The field of thermo- and pH-sensitive copolymers, with applications in controlled drug delivery, is enriched with the copolymer based on N-vinylcaprolactam and maleic acid (VCL–MAc) that is synthesized and characterized in this paper. Cloud point measurements and dynamic light scattering are used to characterize the phase transition of VCL–MAc copolymers with variable composition in aqueous solution. The lower critical solution temperature (LCST) increases when the maleic acid content in the copolymer rises. Also, the LCST strongly depends on the polymer concentrations and the pH of the aqueous solution. The influence of the pH, and as a result of the polyelectrolyte dissociation, on the macromolecular chains conformation is studied by viscometric measurements. An interplay between Coulombic, hydrophobic and hydrogen bonding interactions determines the conformation of the macromolecules in solution and also the phase separation of VCL–MAc copolymers.

Influence of the Comonomer on the Dissociation of Some Alternating Maleic Acid Copolymers

Five alternating copolymers of maleic acid with N-vinylpyrrolidone, vinyl acetate, styrene, 2-vinylnaphthalene, and vinyl cyclohexane were used in order to study the influence of the comonomer on the polyelectrolyte behavior. The dissociation of the maleic acid copolymers was investigated by electrochemical methods in pure water and in the presence of supporting electrolytes. The conformational modifications during the dissociation were directly investigated by viscosimetry and fluorescence probing. The shape of the potentiometric and conductometric titration curves was influenced by the comonomer structure. In salt-free solution, only the first dissociation step was observed. The addition of univalent counterions permitted the evidencing of the second ionization step only for the copolymers with hydrophilic comonomers, but the addition of divalent counterions permitted the evidencing of the second ionization step for all five copolymers. The apparent dissociation constants increase with the increase of the comonomer hydrophobicity. A conformational transition was evidenced especially in the case of the maleic acid-2-vinylnaphthalene copolymer.

Dual-responsive hydrogels based on maleilated curdlan-graft-poly(N-isopropylacrylamide)

ABSTRACT The esterification reaction between curdlan and maleic anhydride was performed to provide polymerizable double bonds and pH-sensitive carboxylic groups for the curdlan chains. The new derivative was used as macromolecular cross-linker in the polymerization of N-isopropylacrylamide, when thermo and pH-sensitive networks were obtained in the form of microparticles. The loading and releasing profiles of a model macromolecular drug, lysozyme, were evaluated. The protein release rate was influenced by the pH and temperature. The pulsatile release of the lysozyme was also observed, the pulse being the swelling of the microparticles due to the decrease of the temperature under the volume phase transition temperature. GRAPHICAL ABSTRACT

Investigation of Interpolymer Complexation Between Poly(Vinylcaprolactam) and Poly(Maleic Acid-Alt-Styrene)

ABSTRACT The interactions between two synthetic polymers used in biomedical applications, maleic acid-styrene copolymer (MAc-St) and poly(vinylcaprolactam) (PVCL), were investigated in dilute aqueous solution considering the influence of the pH, the added salt and the ratio between the components in the mixture. Hydrogen-bonding interactions between the COOH groups of MAc-St and the C═O groups of PVCL, together with hydrophobic interactions are involved in the formation of the interpolymer complex. The complex is insoluble below pH = 2.85 in aqueous solution, but the addition of NaCl enlarged the pH domain where the precipitation of the complex occurred. When the ratio between the polymers was varied, two maxima of the optical density were obtained: at a 1:1 ratio between the COOH and caprolactam groups, and also at a lower ratio (1:3). Other investigations, like the measurements of the turbidity in situ during mixing, and fluorescence, viscometric and potentiometric measurements were performed in order to understand these interactions. The phase separation of the thermosensitive poly(vinylcaprolactam) in the presence of MAc-St was also studied. The cloud point and the phase transition profile were found to be influenced by the amount of polyacid, as well as by the pH.