Hydroxyapatite-loaded macroporous calcium alginate hydrogels: Preparation, characterization, and in vitro evaluation.

Hydrogels from natural polysaccharides are of great interest for tissue engineering. This study aims (1) to prepare hydroxyapatite-loaded macroporous calcium alginate hydrogels by novel one-step technique using internal gelation in water-frozen solutions; (2) to evaluate their physicochemical properties; (3) to estimate their ability to support cell growth and proliferation in vitro. The structure of the hydrogel samples in a swollen state was studied by confocal laser scanning microscopy and was shown to represent a system of interconnected macropores with sizes of tens micron. The swelling behavior of the hydrogels, their mechanical properties (Young's moduli) in function of a hydroxyapatite content (5-30 mass%) were studied. All hydrogel samples loaded with hydroxyapatite were found to support growth and proliferation of mouse fibroblasts (L929) at long-term cultivation for 7 days. The obtained macroporous composite Ca-Alg-HA hydrogels could be promising for tissue engineering.

Nanoaggregates of Biphilic Carboxyl-Containing Copolymers as Carriers for Ionically Bound Doxorubicin.

Application of nanocarriers for drug delivery brings numerous advantages, allowing both minimization of side effects common in systemic drug delivery and improvement in targeting, which has made it the focal point of nanoscience for a number of years. While most of the studies are focused on encapsulation of hydrophobic drugs, delivery of hydrophilic compounds is typically performed via covalent attachment, which often requires chemical modification of the drug and limits the release kinetics. In this paper, we report synthesis of biphilic copolymers of various compositions capable of self-assembly in water with the formation of nanoparticles and suitable for ionic binding of the common anticancer drug doxorubicin. The copolymers are synthesized by radical copolymerization of N-vinyl-2-pyrrolidone and acrylic acid using n-octadecyl-mercaptan as a chain transfer agent. With an increase of the carboxyl group's share in the chain, the role of the electrostatic stabilization factor of the nanoparticles increased as well as the ability of doxorubicin as an ion binder. A mathematical description of the kinetics of doxorubicin binding and release is given and thermodynamic functions for the equilibrium ionic binding of doxorubicin are calculated.

Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel.

Co-delivery of chemotherapeutics in cancer treatment has been proven essential for overcoming multidrug resistance and improving the outcome of therapy. We report the synthesis of amphiphilic copolymers of N-vinyl-2-pyrrolidone and allyl glycidyl ether of various compositions and demonstrate that they can form nanoaggregates capable of simultaneous covalent immobilization of doxorubicin by the epoxy groups in the shell and hydrophobic-driven incorporation of paclitaxel into the core of nanoparticles. The structure of the obtained copolymers was characterized by 13C NMR, IR, and MALDI spectroscopy, as well as adsorption at the water/toluene interface. A linear increase in the number-average molecular weight of amphiphilic copolymers and a decrease in the number-average diameter of macromolecular aggregates with an increase in the ratio N-vinyl-2-pyrrolidone/allyl glycidyl ether were observed. The assembled nanocarriers were characterized by DLS. The reported novel nanocarriers can be of interest for delivery and co-delivery of a wide range of pharmacological preparations and combined therapy for cancer and other deceases.

Formation of Hydrogels Based on a Copolymer of N-Vinyl-2-pyrrolidone and Glycidyl Methacrylate in the Presence of the Reaction Product of 1,3-Dimethylmidazolium Dimethylphosphate and Elemental Sulfur.

The aim of the study is to search for a reaction that provides the possibility of tandem "one-pot" formation of polymer networks during radical copolymerization of N-vinyl-2-pyrrolidone and glycidyl methacrylate. It was shown that the addition of recently synthesized 1,3-dimethylimidazolium (phosphonooxy-)oligosulfanide makes it possible to obtain a cross-linked copolymer in one stage as a result of radical copolymerization of N-vinyl-2-pyrrolidone and glycidyl methacrylate with a molar ratio of monomers less than 1.4. The structure of the copolymerization products of N-vinyl-2-pyrroldione and glycidyl methacrylate formed in the presence of 1,3-dimethylimidazolium (phosphonooxy-)oligosulfanide was characterized by 1H NMR, FTIR and MALDI spectroscopy. 1H NMR spectroscopy revealed an interaction under moderate heating between glycidyl methacrylate and 1,3-dimethylimidazolium (phosphonooxy-)oligosulfanide, accompanied by the formation of a mixture of unsaturated products of complex structure, presumably acting as crosslinking agents. It is shown that when the molar ratio of N-vinyl-2-pyrroldione/glycidyl methacrylate comonomers is 0.89, a densely crosslinked copolymer is formed, capable of limited swelling in water with a velocity constant of 5.06 × 10-2 min-1 and an equilibrium degree of swelling of about 227%.

Chemical Oxidative Polymerization of Methylene Blue: Reaction Mechanism and Aspects of Chain Structure.

The kinetic regularities of the initial stage of chemical oxidative polymerization of methylene blue under the action of ammonium peroxodisulfate in an aqueous medium have been established by the method of potentiometry. It was shown that the methylene blue polymerization mechanism includes the stages of chain initiation and growth. It was found that the rate of the initial stage of the reaction obeys the kinetic equation of the first order with the activation energy 49 kJ × mol-1. Based on the proposed mechanism of oxidative polymerization of methylene blue and the data of MALDI, EPR, and IR spectroscopy methods, the structure of the polymethylene blue chain is proposed. It has been shown that polymethylene blue has a metallic luster, and its electrical conductivity is probably the result of conjugation over extended chain sections and the formation of charge transfer complexes. It was found that polymethylene blue is resistant to heating up to a temperature of 440 K and then enters into exothermic transformations without significant weight loss. When the temperature rises above 480 K, polymethylene blue is subject to endothermic degradation and retains 75% of its mass up to 1000 K.

Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for tissue engineering: Preparation and in vitro evaluation.

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample.

Delta-sleep inducing peptide entrapment in the charged macroporous matrices.

Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2-6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process.

Preparation and characterization of amphiphilic poly-N-vinylpyrrolidone nanoparticles containing indomethacin.

Amphiphilic poly-N-vinylpyrrolidone derivatives (Amph-PVP) with different molecular weight of hydrophilic PVP fragment and one terminal hydrophobic n-alkyl fragment of different length were synthesized for preparation of nano-scaled particles in aqueous media. To estimate novel polymer efficiency and perspective as basis for drug delivery systems, the polymeric micelle-like particles were prepared by dialysis and solvent evaporation methods. Indomethacin was incorporated into hydrophobic inner core of these nanoparticles as a typical model drug. From the dynamic light-scattering measurements, the size of particles formed was less than 200 nm with narrow monodisperse size distribution and nanoparticles size slightly increased with the amount of indomethacin encapsulated into inner core of Amph-PVP particles. The critical aggregation concentration values for prepared polymer samples determined by fluorescence spectroscopy were in micromole range which is lower than it is for common low molecular weight surfactants. As the hydrophobic fragment of amphiphilic polymer increased, the critical aggregation concentration values decreased. An increase of polymer hydrophilic fragment molecular weight produced larger nanoaggregates. In vitro release experiments using indomethacin-loaded Amph-PVP nanoparticles exhibited the sustained release behavior without any burst effect for most polymer samples.