One-Step Preparation of Carboxymethyl Cellulose-Phytic Acid Hydrogels with Potential for Biomedical Applications.

Hydrogels based on natural, biodegradable materials have gained considerable interest in the medical field due to their improved drug delivery profiles and tissue-mimicking architecture. In this regard, this study was devoted to the preparation and characterization of new physically crosslinked hydrogels based on carboxymethyl cellulose and an unconventional crosslinking agent, phytic acid. Phytic acid, in addition to its antioxidant and antibacterial effects, can improve the biological properties and stability of gels, without adding toxicity. Fourier transform infrared (FTIR) spectroscopy, rheological studies and thermal analysis confirmed the hydrogel formation. The influence of the ratio between the cellulose derivative and the crosslinker upon the morphological structure and water uptake was evidenced by scanning electron microscopy (SEM) and swelling measurements in simulated body fluids. Furthermore, procaine was entrapped within the hydrogels and used as a model drug for in vitro studies, which highlighted the dependence of the drug release on the phytic acid content of the matrix. The materials demonstrated antibacterial effects against Escherichia coli and Staphylococcus aureus bacteria. The biocompatibility was assessed on fibroblast cells, and according to our results, hydrogels can improve cell viability highlighting the potential of these systems as therapeutic scaffolds for skin tissue engineering.

New Hydrogel Network Based on Alginate and a Spiroacetal Copolymer.

This study reports a strategy for developing a biohybrid complex based on a natural/synthetic polymer conjugate as a gel-type structure. Coupling synthetic polymers with natural compounds represents an important approach to generating gels with superior properties and with potential for biomedical applications. The study presents the preparation of hybrid gels with tunable characteristics by using a spiroacetal polymer and alginate as co-partners in different ratios. The new network formation was tested, and the structure was confirmed by FTIR and SEM techniques. The physical properties of the new gels, namely their thermal stability and swelling behavior, were investigated. The study showed that the increase in alginate content caused a smooth increase in thermal stability due to the additional crosslinking bridges that appeared. Moreover, increasing the content of the synthetic polymer in the structure of the gel network ensures a slower release of carvacrol, the encapsulated bioactive compound.

Alginate enriched with phytic acid for hydrogels preparation.

Alginate hydrogels are extremely versatile and flexible biomaterials, with an enormous potential for bio-applications use. Their similarity with extracellular matrix is a key factor in their performance for cell and tissue regeneration. In this study superabsorbent high porous hydrogels based on sodium alginate physical crosslinked with a natural crosslinker compound namely phytic acid were prepared and evaluated from the viewpoint of their specific properties. The resulting hydrogels obtained with different ratios between alginate and phytic acid were characterized by Fourier transform infrared spectroscopy technique, scanning electron microscopy, XRD measurements, swelling tests in physiological environment, and thermal analysis by using a simultaneous TG/FT-IR/MS system. There are put into evidence the differences in physico-chemical properties of the hydrogels in relation with their composition, which endows them tunable properties and versatility.

Synthesis of Poly(Ethylene Brassylate-Co-squaric Acid) as Potential Essential Oil Carrier.

Bio-based compounds are a leading direction in the context of the increased demand for these materials due to the numerous advantages associated with their use over conventional materials, which hardly degrade in the environment. At the same time, the use of essential oils and their components is generated mainly by finding alternative solutions to antibiotics and synthetic preservatives due to their bioactive characteristics, but also to their synergistic capacity during the manifestation of different biological properties. The present study is devoted to poly(ethylene brassylate-co-squaric acid) (PEBSA), synthesis and its use for thymol encapsulation and antibacterial system formation. The synthesized copolymer, performed through ethylene brassylate macrolactone ring-opening and copolymerization with squaric acid, was physicochemical characterized. Its amphiphilic character allowed the entrapment of thymol (Ty), a natural monoterpenoid phenol found in oil of thyme, a compound with strong antiseptic properties. The copolymer chemical structure was confirmed by spectroscopic analyses. Thermal analysis evidenced a good thermal stability for the copolymer. Additionally, the antimicrobial activity of PEBSA_Ty complex was investigated against eight different reference strains namely: bacterial strains-Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Enterococcus faecalis ATCC 29212, Klebsiella pneumonie ATCC 10031 and Salmonella typhimurium ATCC 14028, yeast strains represented by Candida albicans ATCC10231 and Candida glabrata ATCC 2001, and the fungal strain Aspergillus brasiliensis ATCC9642.

Stimuli Responsive Scaffolds Based on Carboxymethyl Starch and Poly(2-Dimethylaminoethyl Methacrylate) for Anti-Inflammatory Drug Delivery.

The purpose of the study is to obtain multicomponent polyelectrolyte hydrogels with optimal synergistic properties by combining a modified starch with a synthetic one. Thus, new low-cost and biocompatible semi-interpenetrating polymer network (semi-IPN) hydrogels of carboxymethyl starch and poly(2-dimethylaminoethyl methacrylate) are prepared and investigated. The synthesized hydrogels are studied with respect to the specific characteristics of the gels: swelling kinetics, thermal analysis, viscoelastic characteristics, and their ability to be used as a matrix in drug delivery systems. Therefore, the semi-IPN gels are loaded with ibuprofen, followed by additional tests to assess the in vitro drug release. The cytocompatibility of the hydrogels with respect to their composition is evaluated in vitro on fibroblast cell culture. The investigations confirm the obtainment of new semi-IPN hydrogels with pH and temperature responsiveness, good mechanical strength, and potential for use as drug delivery systems or transdermal patches.

Interpenetrated polymer network with modified chitosan in composition and self-healing properties.

Smart hydrogels endowed with self-healing performance, enhanced stability and unique environmental responsiveness were prepared by interpenetrating the crosslinked poly(2-dimethylaminoethyl methacrylate) between the chains of the water-soluble maleoyl-chitosan. The influence of the ratio between the modified polysaccharide and the homopolymer upon the morphological structure and water uptake behaviour of the hydrogels was put in evidence by Scanning electron microscopy and swelling measurements in simulated body fluids. In addition, the synthesised compounds exhibited responsive properties, self-healing behaviour, and great availability like drug delivery systems. The in vitro study evidenced the dependence of the released procaine on the MAC content in the hydrogels, the release mechanism being controlled mainly by Fickian diffusion. The cytotoxicity assay on fibroblast demonstrated improved viability of cells by increasing the modified polysaccharide ratio into hydrogels. The self-repair capacity along with dual pH/thermo-responsiveness and biocompatibility of the hydrogels demonstrate their viability for various bio-applications.

Evaluation of the Rosemary Extract Effect on the Properties of Polylactic Acid-Based Materials.

New multifunctional materials containing additives derived from natural resources as powdered rosemary ethanolic extract were obtained by melt mixing and processed in good conditions without degradation and loss of additives. Incorporation of powdered rosemary ethanolic extract (R) into poly(lactic acid) (PLA) improved elongation at break, rheological properties, antibacterial and antioxidant activities, in addition to the biocompatibility. The good accordance between results of the chemiluminescence method and radical scavenging activity determination by chemical method evidenced the increased thermoxidative stability of the PLA biocomposites with respect to neat PLA, with R acting as an antioxidant. PLA/R biocomposites also showed low permeability to gases and migration rates of the bioactive compounds and could be considered as high-performance materials for food packaging. In vitro biocompatibility based on the determination of surface properties demonstrated a good hydrophilicity, better spreading and division of fibroblasts, and increased platelet cohesion. The implantation of PLA/R pellets, was proven to possess a good in vivo biocompatibility, and resulted in similar changes in blood parameters and biochemical responses with the control group, suggesting that these PLA-based materials demonstrate very desirable properties as potential biomaterials, useful in human medicine for tissue engineering, wound management, orthopedic devices, scaffolds, drug delivery systems, etc. Therefore, PLA/R-based materials show promising properties for applications both in food packaging and as bioactive biomaterials.

Interpenetrating polymer network systems based on poly(dimethylaminoethyl methacrylate) and a copolymer containing pendant spiroacetal moieties.

The interpenetrating polymer networks (IPNs) are promising materials due to their unique properties. In this context, in the present study, new IPN structures based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) and poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5] undecane) (PITAU) were synthesized. The double network was prepared by synthesizing and crosslinking (with N, N'-methylenebis(acrylamide)) PDMAEMA in the presence of a preformed PITAU network. The effect of the two components upon some properties such us: viscoelasticity, thermal stability and swelling behavior of the new prepared gels were deeply investigated. The viscoelastic parameters indicated stronger networks for PDMAEMA/PITAU hydrogels as compared with PDMAEMA. The thermal parameters also indicate that the IPNs are more stable than PDMAEMA. The IPNs present an increased sensitivity to temperature and pH, the equilibrium swelling degree being strongly influenced by them. This behaviour highlights the possibility of controlling the release of therapeutic agents by swelling and deswelling cycles of the IPNs at different pH and temperatures, depending on composition and the application envisaged.

Scaffolds Based on Collagen, Hyaluronan and Sericin with Potential Applications as Controlled Drug Delivery System.

Natural proteins have been extensively studied as matrices for tissue engineering, due to their excellent biocompatibility and biological properties associated with increasing cell proliferation. By generating complex materials, cell and tissue functions can be tailored to obtain a specific direction, according to the medical needs. The aim of this paper was to obtain scaffolds based on collagen, hyaluronan and sericin, with morphology and physical-chemical properties adequate for controlled drug delivery systems. In this aim various tests were performed: in vitro swelling and degradation studies, Fourier Transform Infrared spectroscopy (FT-IR), Scanning Electronic Microscopy (SEM) and thermogravimetric analysis. Loading and releasing of ibuprofen is also discussed. The results indicate that scaffolds based on collagen, hyaluronan and sericin have a porous structure, strength and stability adequate for skin tissue engineering. The obtained scaffolds swell, degrade and have controlled drug release properties in simulated biological fluids.

The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination.

OBJECTIVES: The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations. METHODS: The oral tablets were made by using a Christ freeze-dryer alpha 2-4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams. RESULTS: FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets. CONCLUSION: In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the 'codrug' complex, which do not affect the release of the bioactive compounds.

Hybrid gels by conjugation of hyaluronic acid with poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)undecane) copolymers.

The approach of covalent conjugation for coupling synthetic polymers with biomolecules represents an appealing strategy to produce new compounds with distinctive properties for biomedical applications. In the present study we generated hybrid gels with tunable characteristics by using hyaluronic acid (HA) and four variants of poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5] undecane) (PITAU) copolymers, differing through the molar ratios between comonomers. The new bioconjugate compounds were realized by using a ″grafting to″ strategy, for further ensuring new ways for coupling of various bioactive compounds, taking into account that the grafted copolymers are dual sensitive to pH and temperature. The procedure of chemical crosslinking, by opening the anhydride cycle of the copolymer with the hydroxyl groups of hyaluronic acid, was used to prepare the bioconjugates. The chemical conjugation between HA and PITAU copolymers, as well as the structure of the new compounds, was confirmed by FTIR and NMR techniques. The physical properties of the new gels as thermal stability, swelling capacity, and rheological properties were investigated. The bioconjugate networks were also investigated as drug delivery carriers by using indomethacin as a model drug. In vitro and in vivo tests attested the homogeneity of the bioactive compounds as well as a good biochemical response, showing good biocompatibility for the new structures.

Multifunctional nanogels with dual temperature and pH responsiveness.

Over the last 10 years, the development of intelligent biomaterials for medical and pharmaceutical applications has attracted growing interest by combining interdisciplinary efforts. Between them nanogels represent one of the most attractive carriers for innovative drug delivery systems. In the present investigation new variants of multi-responsive nanogels have been synthesized by crosslinking poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5] undecane) copolymer (having different molar ratios between comonomers) with 1,12-dodecandiol. The new structures were obtained by using modification of itaconic anhydride moieties in the copolymer. This is a convenient method for the preparation of a network with increased functionality, which further may ensure new strategies for coupling various bioactive compounds, especially owing to the behavior of the used copolymers, which present dual pH and temperature sensitive characteristics. The chemical structure of the new compounds was confirmed by FTIR and 1H RMN spectra. Also, the evaluation of thermal stability by thermogravimetric analysis sustains the covalent bonds occurring between the copolymer and diol. The dual responsiveness of the nanogel structures to temperature and pH was put into evidence by DLS studies. This feature can be used for the development of drug delivery systems, which can mimic biological response behavior to a certain extent. The new synthesized nanogels were tested as drug delivery systems by using diclofenac as a model drug. The results obtained from in vitro and in vivo investigation confirm the bioactivity of the nanogel networks.

Biodegradation of poly(lactic acid) and some of its based systems with Trichoderma viride.

The purpose of this study was to assess the biodegradation of poly(lactic acid) (PLA) and some plasticized PLA based systems by Trichoderma viride fungus, in liquid medium and controlled laboratory conditions. The studied systems were achieved using PLA, hydrolyzed collagen (HC) as biological macromolecules and other additives by melt processing procedure. PLA and the systems' biodegradability was examined by the weight losses of the samples (after 7 and 21 days of exposure) and FTIR-ATR, GPC, SEM analyses (after 21 fungus inoculation days). The thermogravimetry (TG-DTG) study showed that the thermostability of the samples decreased after biodegradation and was influenced by the chemical structure of the systems' components.

Upon synthesis of a polymeric matrix with pH and temperature responsiveness and antioxidant bioactivity based on poly(maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5] undecane) derivatives.

Poly(maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5] undecane), acquired through radical polymerization, was synthesized with the aim to prepare an alternant copolymer with precise placement of functional groups along the polymer backbones. The new structure owing to the suitable and specific functionalities is anticipated to be used as reactive polymer to link bioactive compounds via maleic anhydride moiety. The copolymer was improved in its functionality by maleic anhydride ring opening with different amounts of erythritol in order to confer antioxidant characteristics to the polymeric structure. The chemical structure of the new prepared polymers was confirmed by FTIR and (1)H NMR spectra, and the polymers were also characterized from the viewpoint of their thermal stability. The dual sensitivity of the polymeric structure, at temperature and pH, was evaluated by determining the hydrodynamic radius and zeta potential in interdependence with the environment conditions. The polymer morphology was investigated by SEM. The antioxidant character was evaluated measuring the scavenger properties of the functionalized copolymer with erythritol against the 2,2-diphenyl-1-picrylhydrazyl radicals. The acute toxicity investigation, realized in vivo for the copolymer and the derivatives, allows the inclusion of the compounds into the group of moderately toxic accordingly to Hodge and Sterner toxicity scale owing to the lethal dose 50 determined values.

Obtaining of new magnetic nanocomposites based on modified polysaccharide.

The study presents the preparation of some composite materials with magnetic properties by two different encapsulation methods of magnetite (Fe3O4) in a polymer matrix based on carboxymethyl starch-g-polylactic acid (CMS-g-PLA). The copolymer matrix used to obtain the magnetic nanocomposites was synthesized by grafting reaction of carboxymethyl starch (CMS) with D,L-lactic acid (DLLA), in the presence of Sn octanoate [Sn(Oct)2] as catalyst. Magnetite was obtained by co-precipitation from aqueous salt solutions FeCl2/FeCl3 (molar ratio 1/2). The magnetic composites were prepared by precipitation method in acetone (non-solvent) of the DMSO solutions of magnetite and copolymer, and synthesis in situ of the nanocomposites. In the first case, the particle size measured by DLS-technique was 168 nm, and the magnetization was 46.82 emu/g, while after in situ synthesis, the composite materials showed smaller size (141 nm), but the magnetization was reduced (3.04 emu/g). The higher magnetization in the first case is due to the great degree of encapsulation of the magnetite, which was about 43.4 wt.%, compared to 4.37 wt.% for the in situ synthesis (determined by thermogravimetry). The CMS-g-PLA copolymer, magnetite, and the nanocomposites were characterized by infrared spectroscopy (FTIR), near infrared chemical imagistic (NIR-CI), dynamic light scattering (DLS) technique, X-ray diffraction (WAXD), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM) and thermal analyses. Since the polymer matrix and magnetite are biodegradable and biocompatible, the magnetic nanocomposites can be used for conjugation of some drugs. The polymer matrix CMS-g-PLA acts as a shell, and vehicle for the active component, whereas magnetite is the component which makes targeting possible by external magnetic field manipulation.