Manuela T. Nistor

Hybrid collagen-based hydrogels with embedded montmorillonite nanoparticles.

Montmorillonite nanoparticles have been physically incorporated within a crosslinked collagen/poly(N-isopropyl acrylamide) network in order to adjust the properties of the stimuli-responsive hybrid systems. The research underlines both the influence of hydrogel composition and nanoparticle type on hybrid hydrogel properties. The dispersion of the montmorillonite nanoparticles in polymeric matrix have been visualized by SEM, TEM and AFM techniques and quantitatively and qualitatively estimated using near infrared chemical imaging. The electrical charge of the nanoparticles influenced the polymeric chain arrangement and the pore size. The morphologies of the nanoparticulated layers are partially exfoliated or intercalated and uniformly dispersed through the polymeric semi-interpenetrated network based on collagen and poly(N-isopropyl acrylamide). The hybrid hydrogels exhibit pseudoplastic behavior and the addition of nanoparticles has resulted in the increase of the complex viscosity. The adhesion capacity was affected mainly by the presence of organically modified montmorillonites.

Biocompatibility, biodegradability, and drug carrier ability of hybrid collagen-based hydrogel nanocomposites

The biocompatibility, biodegradability, and drug carrier capacity of new types of hybrid hydrogels were evaluated for potential medical applications. The effects of swelling and deswelling of the hybrid hydrogels on drug loading and release capacity were evaluated. The hybrid hydrogels with Dellite® 67G and Cloisite® 93A had superior collagenase resistance compared to hydrogels without the inorganic nanoparticles. The effect of the hybrid hydrogels on the immune response parameters was followed by evaluating the chronic inflammation in rats. These hybrid hydrogels have the potential for medical and pharmaceutical applications as well as for scaffolds production in the reconstruction and regeneration of burned tissues with control of inflammatory processes.

Characterization of the semi-interpenetrated network based on collagen and poly(N-isopropyl acrylamide-co-diethylene glycol diacrylate).

The study is devoted to the characterization of the semi-interpenetrating polymeric network (semi-IPN) structures, prepared as dual sensitive networks, based on poly(N-isopropyl acrylamide-co-diethylene glycol diacrylate) inserted into a collagen porous membrane with potential biomedical-applications. The pharmaceutical applications are related to the possibility of using the semi-synthetic networks for inclusion, retention, transportation and release of drug molecules. The insertion and the homogeneity distribution of the drug into the polymeric network were evaluated by near infrared-chemical imaging (NIR-CI) technique. The drug release was investigated from the kinetically viewpoint in simulated biological environment by using UV-vis spectrophotometric technique. The zeta potential measurement results showed meaningful change of the electric potential of the network surface at the interfacial double layer with the environment in the interdependence with the network composition and environment characteristics. The biodegradable character of the semi-synthetic network, also presented, undergoes with tissue engineering request for achievement of tissue substituents. Texture analysis of the semi-IPN was realized in order to evidence the potential applications of the prepared compounds in tissue engineering. The adhesion properties reveal the possibility to control the surface adhesion by: network composition, the ratio between the polymer types, and the crosslinking degree of polymeric networks. The evaluation of the semi-IPN characteristics in medical terms, concerned the surface electrical charge, the loading, retention and release properties of an active compound, the adhesion properties and the effect of collagenase enzyme over the collagen fibres as component in semi-IPN, and from the pharmaceutical terms emphasizes the potential applications of the new polymeric semi-IPN networks.

Immunoglobulin G immobilization on PVDF surface

Immobilization of antibody molecules onto hydrophobic polymeric surfaces with disordered orientation is something unwanted in many applications. To overcome this drawback, controlled immunoglobulin G (IgG) immobilization onto poly(vinylidene fluoride) surface was investigated in this paper. A two-step process involving radiofrequency plasma pretreatment for polymer surface functionalization, followed by coupling reaction was developed, after which immunoglobulin G was immobilized onto the surface directly or via protein-A. IR and XPS data proved that the process is more efficient when the radiofrequency plasma pretreatment was performed using N2 and N2/H2 as discharge gases. NIR-CI, AFM and XPS surface evaluation revealed that immobilization of IgG onto N2/H2 plasma-treated PVDF via grafted protein-A was achieved with an ends-on orientation, leaving available the antigen binding sites of IgG. This procedure could be a promising route for the preparation of oriented IgG assembly onto PVDF, useful in biomedical, membranes or sensors applications. QCM results showed a better antibody-antigen interaction when IgG immobilization onto PVDF substrate is mediated by protein A.

Indomethacin uptake into poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2, 4,8,10-tetraoxaspiro (5.5)-undecane) network: In vitro and in vivo controlled release study

Networks based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane), synthesized through radical dispersion polymerization, were used as template for indomethacin (INN) as model drug. The copolymers were characterized by swelling studies at three pH values (2.4, 5.5 and 7.4) and two temperatures (room temperature 24 °C and physiological temperature 37 °C). Fourier transform infrared (FTIR) spectroscopic analysis was used to sustain the copolymer structures. Scanning electron microscopy (SEM) and thermogravimetric (TG) investigations were used to examine microstructure and appreciate the thermal stability of the polymer samples. The studies of the INN drug release from the copolymer networks were in vitro performed. The in vivo study results (biocompatibility tests, somatic nociceptive experimental model (tail flick test) and visceral nociceptive experimental model (writhing test)) are also reported in this paper.

Upon some multi-membrane hydrogels based on poly( N , N -dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) Undecane): preparation, characterization and in vivo tests

The study presents the possibility of preparation of multi-membrane gel systems with different morphologies and properties, based on poly(N,N-dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane) copolymer and crosslinked with N,N′-methylene-bis-acrylamide. The basic copolymer has dual thermo- and pH sensitive character. After the core hydrogel is realized, the preformed gel is immersed in the aqueous solutions of ammonia, sodium chloride and sodium citrate for further edge constructing of the supramolecular assemblies. Then, the new layers by adding new sets of gelifying components are realized. The new multi-membrane gel systems are intended to be used as matrix for bioactive substances embedding. In this context the systems were loaded with norfloxacin as drug model. The in vivo tests show good biocompatibility for the implants based on multi-membrane gel structures loaded with drug.

Semi-imprinting Quercetin into Poly[N,N-Dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-Tetraoxaspiro (5.5) Undecane] Network: Evaluation of the Antioxidant Character

A responsive antioxidant system constituted from quercetin inserted into poly[N,N-dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane] through a semi-imprinted procedure was evaluated. A continuous magnetic field (MF) was used during supramolecular structure preparation. The strength of coupling quercetin was evaluated based on the template release from the polymeric matrices, as well as to what extent quercetin reloaded into the polymer matrix in prescribed conditions--with or without the MF presence--shows antioxidant properties. The antioxidant activity of the complex was investigated by radical inhibitor activity method using 2, 2-diphenyl-l-picrylhydrazyl. The evaluation of the homogeneity distribution of the quercetin inside the polymeric network was made by near-infrared chemical imaging and correspondingly statistical analysis. For in vivo biocompatibility investigation, granuloma test in rats was performed correlated with the activity of enzymes involved in oxidative stress as well as immunologic effects of tested supramolecular complexes that include quercetin as therapeutic agent.

Evaluation of the controlled release ability from the poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]-undecane) polymer network synthesized in the presence of β-cyclodextrin

The study presents the possibility to use the 2-hydroxyethyl methacrylate—HEMA copolymer with a comonomer with spiroacetal moiety, 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]-undecane)-U, as polymer network for loading the indomethacin—INN as drug model, and also, the controlled release evaluation of the prepared bioactive system. The macromolecular compounds were prepared by radical dispersion polymerization in the presence of a pair of surfactants. The use of cyclodextrin as surfactant allowed the building of the host–guest complexes by inclusion of hydrophobic molecules. Also, the cyclodextrin supplemented the hydrogen bonds and the hydrophobic interactions responsible for the stability of the achieved complexes. The copolymers composition and the INN inclusion onto the polymeric matrix were confirmed by FTIR analysis. The porous structure of the lyophilized P(HEMA-U) samples was illustrated by SEM images. The swelling studies evidenced the interdependence between P(HEMA-U) network properties and the spiroacetal moiety amount. Thus, the copolymers presented the increase of the equilibrium swelling degree with pH and temperature. Also, the polymeric matrices manifested dual sensitivity with pH and temperature. The in vitro release of the INN drug from the polymeric network as well as the in vivo experimental studies evidenced the benefit consequence of the spiroacetal compound presence. The clinical observation of the experimental groups does not show any behavioral modifications to suggest a possible toxic effect of these polymeric formulations with and without INN.

Stimuli Responsive Matrices for Medical Applications

Different types of stimuli responsive polymers that respond with a property change to a variation in the environmental conditions are an attractive class of materials for advanced applications in biomedical or pharmaceutical fields. Three types of responsive biocompatible and biodegradable polymer matrices are presented as potential biomaterials for medical application as carriers for various drugs and tissue engineering substitutes. Hybrid hydrogels based on collagen/ N-isopropyl acrylamide containing montmorillonite nanoparticles are promising materials for tissue engineering and also as carriers for norfloxacin, a chemotherapeutic antibacterial agent. Semi-interpenetrated hydrogels based either on substituted anhydride modified collagen and 2-hydroxyethyl methacrylate or on alginate and poly (N-isopropylacrylamide) were tested as matrices for the controlled delivery of bisoprolol fumarate, an antihypertensive drug and respectively of ketoprofen, a non-steroidal anti-inflammatory drug.