Mucoadhesive interactions of amphiphilic cationic copolymers based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride.

Three series of water-soluble cationic copolymers have been synthesised by free-radical copolymerisation of [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT) with methyl acrylate (MA), butyl acrylate (BA) and butyl methacrylate (BMA). The interactions between these copolymers and porcine stomach mucin have been studied in aqueous solutions using dynamic light scattering, zeta-potential measurements, turbidimetric titration and transmission electron microscopy (TEM). It was demonstrated that mixing aqueous dispersions of mucin with solutions of the cationic copolymers results in significant changes in size distribution and zeta-potential of its particles. It was found that an increase in the content of hydrophobic groups in copolymers leads to more efficient adsorption of macromolecules on the surface of mucin particles, which evidences the importance of hydrophobic effects in mucoadhesion. The efficiency of mucoadhesive interactions was found to be significantly dependent on pH, which affects the surface charge and aggregation stability of mucin.

Design of mucoadhesive polymeric films based on blends of poly(acrylic acid) and (hydroxypropyl)cellulose.

Mixing of aqueous solutions of poly(acrylic acid) and (hydroxypropyl)cellulose results in formation of hydrogen-bonded interpolymer complexes, which precipitate and do not allow preparation of homogeneous polymeric films by casting. In the present work the effect of pH on the complexation between poly(acrylic acid) and (hydroxypropyl)cellulose in solutions and miscibility of these polymers in solid state has been studied. The pH-induced complexation-miscibility-immiscibility transitions in the polymer mixtures have been observed. The optimal conditions for preparation of homogeneous polymeric films based on blends of these polymers have been found, and the possibility of radiation cross-linking of these materials has been demonstrated. Although the gamma-radiation treatment of solid polymeric blends was found to be inefficient, successful cross-linking was achieved by addition of N,N'-methylenebis(acrylamide). The mucoadhesive potential of both soluble and cross-linked films toward porcine buccal mucosa is evaluated. Soluble films adhered to mucosal tissues undergo dissolution within 30-110 min depending on the polymer ratio in the blend. Cross-linked films are retained on the mucosal surface for 10-40 min and then detach.

pH effects on the complexation, miscibility and radiation-induced crosslinking in poly(acrylic acid)-poly(vinyl alcohol) blends.

The effect of pH on the complexation of poly(acrylic acid) with poly(vinyl alcohol) in aqueous solution, the miscibility of these polymers in the solid state and the possibility for crosslinking the blends using gamma radiation has been studied. It is demonstrated that the complexation ability of poly(vinyl alcohol) with respect to poly(acrylic acid) is relatively low in comparison with some other synthetic non-ionic polymers. The precipitation of interpolymer complexes was observed below the critical pH of complexation (pH(crit1)), which characterizes the transition between a compact hydrophobic polycomplex and an extended hydrophilic interpolymer associate. Films prepared by casting from aqueous solutions at different pH values exhibited a transition from miscibility to immiscibility at a certain critical pH, pH(crit2), above which hydrogen bonding is prevented. It is shown here that gamma radiation crosslinking of solid blends is efficient and only results in the formation of hydrogel films for blends prepared between pH(crit1) and pH(crit2). The yield of the gel fraction and the swelling properties of the films depended on the absorbed radiation dose and the polymer ratio. [Diagram: see text] SEM image of an equimolar PAA-PVA blend cast from a pH 4.6 solution.

Complex formation of linear poly(methacrylic acid) with uranyl ions in aqueous solutions.

The complex formation of uranyl ions (UO(2+)2) with poly(methacrylic acid) (PMAA) was investigated by potentiometric, conductometric, UV-visible, luminescence and FTIR spectroscopic, and thermal analysis methods. The stoichiometric ratio at complexation between polymer and uranyl ions was found to be equal to 2 polymer base units per uranyl ion. FTIR spectra of the PMAA-UO(2+)2 complex confirmed incorporation of metal ions into the polymer and showed that the electrostatic interactions play a major role in complexation. An increase of emission intensity in luminescence spectra of uranyl ions suggests influence of conformation peculiarity of the poly(methacrylic acid) chain. The thermal degradation of polycomplex starts at lower temperature as compared to pristine PMAA that is due to the lower thermal stability of PMAA-UO(2+)2 complex.

Polycomplexes of poly(acrylic acid) with streptomycin sulfate and their antibacterial activity.

Complex formation between streptomycin sulfate and poly(acrylic acid) has been studied in aqueous solutions by turbidimetric, potentiometric and viscometric methods as well as by FTIR spectroscopy. It was shown that these polycomplexes are stabilized by electrostatic interactions. The solubility of polycomplexes was examined as a function of pH and it was found that at pH values below 3.1 the polycomplexes undergo complete dissociation or dissolution. The antimicrobial activity of the drug and its polycomplex was evaluated using Sarcina sp. as a model organism. It was demonstrated that the polycomplexes have an antimicrobial activity on the same level as the free drug.

PH effects in the complex formation and blending of poly(acrylic acid) with poly(ethylene oxide).

The effect of pH on the complex formation between poly(acrylic acid) (PAA) and poly(ethylene oxide) (PEO) has been studied in aqueous solutions by turbidimetric and fluorescent methods. It was shown that the formation of insoluble interpolymer complexes is observed below a certain critical pH of complexation (pH(crit1)). The formation of hydrophilic interpolymer associates is possible above pH(crit1) and below a certain pH(crit2). The effects of polymer concentrations in solution and PEO molecular weight as well as inorganic salt addition on these critical pH values were studied. The polymeric films based on blends of PAA and PEO were prepared by casting from aqueous solutions with different pHs. These films were characterized by light transmittance measurements and differential scanning calorimetry. The existence of the pH value above which the polymers form an immiscible blend was demonstrated. The transitions between the interpolymer complex, miscible blend, and immiscible blend caused by pH changes are discussed. The recommendations for preparation of homogeneous miscible films based on compositions of poly(carboxylic acids) and various nonionic water-soluble polymers are presented.

Polymeric complexes of lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether).

The specific interactions of local anesthetic lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether), as well as in a triple system composed of the drug and both polymers, have been studied in aqueous solutions by viscometric, turbidimetric, potentiometric, and FTIR spectroscopic methods. The mechanism of the drug binding to the polymers and the structures of the polycomplexes formed are clarified.