Semi-Interpenetrating Polymer Networks Based on Hydroxy-Ethyl Methacrylate and Poly(4-vinylpyridine)/Polybetaines, as Supports for Sorption and Release of Tetracycline.

Semi-interpenetrating polymer networks (semi-IPN) represent a type of polymeric material that has gained increasing amount of interest for their potential biomedical application. This study presents the synthesis, characterization and tetracycline loading/release capacities of semi-IPNs based on hydroxyethyl methacrylate (HEMA) and poly(4-vinylpyridine) (P4VP) or poly (1-vinyl-4-(1-carboxymethyl) pyridinium betaine) (P4VPB-1) and poly (1-vinyl-4-(2-carboxyethyl) pyridinium betaine) (P4VPB-2). The optimization of the semi-IPNs synthesis was achieved by studying the influence of reaction parameters (chemical structure of the cross-linking agent, HEMA:crosslinker ratio, HEMA:linear polymers ratio and the type of solvent of the linear polymers) on the yield of obtaining semi-IPNs and swelling capacity of these systems. Fourier-transform infrared analysis and scanning electron microscopy highlighted the chemical structures and morphologies of the semi-IPNs. The higher swelling capacity was observed in the case of the PHEMA/P4VPB-2 network due to the increased hydrophilicity of P4VPB-2 compared with P4VP and P4VPB-1 polymers. In vitro release studies of tetracycline reveal that the release mechanism is represented by non-Fickian diffusion being controlled by both diffusion and swelling processes. The antimicrobial activity of semi-IPN-tetracycline systems was tested against E. coli and S. aureus, demonstrating that tetracycline is released from the semi-IPN and retains its bactericidal activity. An increased value of the inhibition zone diameter compared with that of tetracycline indicates the possibility that the semi-IPN containing P4VPB-2 also exhibits intrinsic antimicrobial activity due to the presence of the polybetaine in the network structure.

Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems.

Crosslinked porous microparticles have received great attention as drug delivery systems lately due to their unique set of properties: the capability to form various polymer-drug combinations, low immunogenicity, patient compliance and ability to release drugs in a delayed or controlled manner. Moreover, polymers with betaine groups have shown some unique features such as antifouling, antimicrobial activity, biocompatibility and strong hydration properties. Herein, novel porous zwitterionic microparticles were prepared in two stages. The first step involves the synthesis of porous microparticles based on glycidyl methacrylate, N-vinylimidazole and triethyleneglycol dimethacrylate using the suspension polymerization technique, the second step being the synthesis of zwitterionic porous microparticles by polymer-analogous reaction in presence of sodium monochloroacetate as betainization agent. Both types of microparticles were characterized structurally and morphologically by FT-IR spectroscopy, energy dispersive X-ray analysis, scanning electron microscopy, dynamic vapors sorption and mercury porosimetry. The tetracycline loading into crosslinked and zwitterionic microparticles was also performed, the maximum tetracycline loading capacities being 87 mg/g and 135 mg/g, respectively. The drug release mechanism, elucidated by various mathematical models, is controlled by both diffusion and swelling processes as a function of the zwitterionic and/or porous microparticle structure. Both types of microparticles presented antibacterial activity against the two reference strains used in this study: Escherichia coli and Staphylococcus aureus.

Grafted Microparticles Based on Glycidyl Methacrylate, Hydroxyethyl Methacrylate and Sodium Hyaluronate: Synthesis, Characterization, Adsorption and Release Studies of Metronidazole.

Three types of precursor microparticles based on glycidyl methacrylate, hydroxyethyl methacrylate and one of the following three crosslinking agents (mono-, di- or triethylene glycol dimethacrylate) were prepared using the suspension polymerization technique. The precursor microparticles were subsequently used to obtain three types of hybrid microparticles. Their synthesis took place by grafting sodium hyaluronate, in a basic medium, to the epoxy groups located on the surface of the precursor microparticles. Both types of the microparticles were characterized by: FTIR spectroscopy, epoxy groups content, thermogravimetric analysis, dimensional analysis, grafting degree of sodium hyaluronate, SEM and AFM analyses, and specific parameters of porous structures (specific surface area, pore volume, porosity). The results showed that the hybrid microparticles present higher specific surface areas, higher swelling capacities as well as higher adsorption capacities of antimicrobial drugs (metronidazole). To examine the interactions between metronidazole and the precursor/hybrid microparticles the adsorption equilibrium, kinetic and thermodynamic studies were carried out. Thus, it was determined the performance of the polymer systems in order to select a polymer-drug system with a high efficiency. The release kinetics reflect that the release mechanism of metronidazole in the case of hybrid microparticles is a complex mechanism characteristic of anomalous or non-Fickian diffusion.

Hydrogel Beads of Amidoximated Starch and Chitosan as Efficient Sorbents for Inorganic and Organic Compounds.

The synthesis of hydrogel beads involving natural polymers is, nowadays, a leading research area. Among natural polymers, starch and chitosan represent two biomolecules with proof of efficiency and low economic impact in various utilization fields. Therefore, herein, the features of hydrogel beads obtained from chitosan and three sorts of starch (potato, wheat and rise starches), grafted with acrylonitrile and then amidoximated, were deeply investigated for their use as sorbents for heavy metal ions and dyes. The hydrogel beads were prepared by ionotropic gelation/covalent cross-linking of chitosan and functionalized starches. The chemical structure of the hydrogel beads was analyzed by FT-IR spectroscopy; their morphology was revealed by optical and scanning electron microscopies, while the influence of the starch functionalization strategies on the crystallinity changes was evaluated by X-ray diffraction. Molecular dynamics simulations were used to reveal the influence of the grafting reactions and grafted structure on the starch conformation in solution and their interactions with chitosan. The sorption capacity of the hydrogel beads was tested in batch experiments, as a function of the beads' features (synthesis protocol, starch sort) and simulated polluted water, which included heavy metal ions (Cu2+, Co2+, Ni2+ and Zn2+) and small organic molecules (Direct Blue 15 and Congo red).

Polybetaines in Biomedical Applications.

Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups) situated in the same structural unit represent an important class of smart polymers with unique and specific properties, belonging to the family of zwitterionic materials. According to the anionic groups, polybetaines can be divided into three major classes: poly(carboxybetaines), poly(sulfobetaines) and poly(phosphobetaines). The structural diversity of polybetaines and their special properties such as, antifouling, antimicrobial, strong hydration properties and good biocompatibility lead to their use in nanotechnology, biological and medical fields, water remediation, hydrometallurgy and the oil industry. In this review we aimed to highlight the recent developments achieved in the field of biomedical applications of polybetaines such as: antifouling, antimicrobial and implant coatings, wound healing and drug delivery systems.

Immobilization and Release Studies of Triazole Derivatives from Grafted Copolymer Based on Gellan-Carrying Betaine Units.

New polymer-bioactive compound systems were obtained by immobilization of triazole derivatives onto grafted copolymers and grafted copolymers carrying betaine units based on gellan and N-vinylimidazole. For preparation of bioactive compound, two new types of heterocyclic thio-derivatives with different substituents were combined in a single molecule to increase the selectivity of the biological action. The 5-aryl-amino-1,3,4 thiadiazole and 5-mercapto-1,2,4-triazole derivatives, each containing 2-mercapto-benzoxazole nucleus, were prepared by an intramolecular cyclization of thiosemicarbazides-1,4 disubstituted in acidic and basic medium. The structures of the new bioactive compounds were confirmed by elemental and spectral analysis (FT-IR and 1H-NMR). The antimicrobial activity of 1,3,4 thiadiazoles and 1,2,4 triazoles was tested on gram-positive and gram-negative bacteria. The triazole compound was chosen to be immobilized onto polymeric particles by adsorption. The Langmuir, Freundlich, and Dubinin-Radushkevich adsorption isotherm were used to describe the adsorption equilibrium. Also, the pseudo-first and pseudo-second models were used to elucidate the adsorption mechanism of triazole onto grafted copolymer based on N-vinylimidazole and gellan (PG copolymer) and grafted copolymers carrying betaine units (PGB1 copolymer). In vitro release studies have shown that the release mechanism of triazole from PG and PGB1 copolymers is characteristic of an anomalous transport mechanism.

The Benefits of Smart Nanoparticles in Dental Applications.

Dentistry, as a branch of medicine, has undergone continuous evolution over time. The scientific world has focused its attention on the development of new methods and materials with improved properties that meet the needs of patients. For this purpose, the replacement of so-called "passive" dental materials that do not interact with the oral environment with "smart/intelligent" materials that have the capability to change their shape, color, or size in response to an externally stimulus, such as the temperature, pH, light, moisture, stress, electric or magnetic fields, and chemical compounds, has received much attention in recent years. A strong trend in dental applications is to apply nanotechnology and smart nanomaterials such as nanoclays, nanofibers, nanocomposites, nanobubbles, nanocapsules, solid-lipid nanoparticles, nanospheres, metallic nanoparticles, nanotubes, and nanocrystals. Among the nanomaterials, the smart nanoparticles present several advantages compared to other materials, creating the possibility to use them in various dental applications, including preventive dentistry, endodontics, restoration, and periodontal diseases. This review is focused on the recent developments and dental applications (drug delivery systems and restoration materials) of smart nanoparticles.

New Grafted Copolymers Carrying Betaine Units Based on Gellan and N-Vinylimidazole as Precursors for Design of Drug Delivery Systems.

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of N-vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/N,N,N',N' tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: ci = 0.08 mol/L, cm = 0.8 mol/L, cp = 8 g/L, tr = 4 h and T = 50 °C. The kinetics of the graft copolymerization of N-vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, 1H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.

Complex calcium carbonate/polymer microparticles as carriers for aminoglycoside antibiotics.

Composite microparticles of CaCO3 and two pectin samples (which differ by the functional group ratio) or corresponding nonstoichiometric polyelectrolyte complexes with different molar ratios (0.5, 0.9 and 1.2) are obtained, characterized and tested for loading and release of streptomycin and kanamycin sulphate. The synthesized carriers were characterized before and after drug loading in terms of morphology (by SEM using secondary electron and energy selective backscattered electron detectors), porosity (by water sorption isotherms) and elemental composition (by elemental mapping using energy dispersive X-ray and FTIR spectroscopy). The kinetics of the release mechanism from the microparticles was investigated using Higuchi and Korsmeyer-Peppas mathematical models.

Autotemplate Microcapsules of CaCO3/Pectin and Nonstoichiometric Complexes as Sustained Tetracycline Hydrochloride Delivery Carriers.

New types of composites were obtained by an autotemplate method for assembling hollow CaCO3 capsules by using pH-sensitive polymers. Five pectin samples, which differ in the methylation degree and/or amide content, and some nonstoichiometric polyelectrolyte complex dispersions, prepared with the pectin samples and poly(allylamine hydrochloride), were used to control the crystal growth. The morphology of the composites was investigated by scanning electron microscopy, and the polymorphs characteristics were investigated by FTIR spectroscopy. The presence of the polymer in the composite particles was evidenced by X-ray photoelectron spectroscopy, particle charge density, and zeta-potential. The new CaCO3/pectin hollow capsules were tested as a possible matrix for a tetracycline hydrochloride carrier. The kinetics of the drug release mechanism was followed using Higuchi and Korsmeyer-Peppas mathematical models.

Surface characterization and drug release from porous microparticles based on methacrylic monomers and xanthan.

Porous crosslinked microparticles based on glycidyl methacrylate and xanthan were prepared by suspension polymerization and used for loading theophylline, a bronhodilatator drug, in order to obtain new drug delivery systems. The surface morphologies observed by means of SEM and AFM analysis demonstrated that microparticles show a spherical shape and are characterized by a porous structure. The presence of xanthan in the structure of microparticles leads to a decrease of surface roughness and pore diameters as well as to an increase of hydrophilicity degree compared to the micropaticles based only on glycidyl methacrylate. To analyze the in vitro release data various mathematical models were used, such as, first order, Higuchi model, Korsmeyer-Peppas model and Baker-Lonsdale model. Based on the highest values of the correlation coefficient, the analysis of the kinetic data indicate that drug release from G1 and X1 porous microparticles fits similarly well to the first order and Higuchi models and diffusion was the dominant mechanism of drug release.

Complex microparticulate systems based on glycidyl methacrylate and xanthan.

Porous microparticles based on glycidyl methacrylate, dimethacrylic monomers [ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate] and xanthan gum were synthesized by aqueous suspension polymerization method in the presence of toluene as diluent using two types of initiators: benzoyl peroxide and ammonium persulfate. The G microparticles based on glycidyl methacrylate and dimethacrylic monomers and X microparticles based on glycidyl methacrylate, xanthan and dimethacrylic monomers were characterized by various techniques including FT-IR spectroscopy, TG analysis, SEM analysis and DVS method. The specific surface areas were determined by DVS method, while the copolymer porosities and pore volume were obtained from the apparent and skeletal densities. The results have indicated that xanthan was included in the crosslinked matrix by means of covalent bonds. X microparticles have a porous structure with higher specific surface area (129-44 m(2)/g) and higher sorption capacities compared with G microparticles (69-31 m(2)/g).

[New polymer-drug systems based on natural and synthetic polymers]. / Noi sisteme polimer-medicament pe baza de polimeri naturali si sintetici.

The great versatility of polymers makes them very useful in the biomedical and pharmaceutical fields. The combination of natural and synthetic polymers leads to new materials with tailored functional properties. The aim of this work consists in the preparation of new drug delivery system based on chitosan (natural polymer) and polybetaines (synthetic polymers), by a simple process, well known in the literature as complex coacervation methods. Also, the adsorption and release studies of two antibiotics as well as the preservation of their bactericidal capacities were performed.