Liliana Verestiuc

Chemical functionalization of hyaluronic acid for drug delivery applications

Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H(1) NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications.

Biomimetic chitosan–calcium phosphate composites with potential applications as bone substitutes: Preparation and characterization†

A novel biomimetic technique for obtaining chitosan-calcium phosphates (Cs-CP) scaffolds are presented: calcium phosphates are precipitated from its precursors, CaCl(2) and NaH(2) PO(4) on the Cs matrix, under physiological conditions (human body temperature and body fluid pH; 37°C and pH = 7.2, respectively). Materials composition and structure have been confirmed by various techniques: elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). FTIR and SEM data have shown the arrangement of the calcium phosphates-hydroxyapatite (CP-Hap) onto Cs matrix. In this case the polymer is acting as glue, bonding the calcium phosphates crystals. Behavior in biological simulated fluids (phosphate buffer solution-PBS and PBS-albumin) revealed an important contribution of the chelation between -NH3(+) and Ca(2+) on the scaffold interaction with aqueous mediums; increased quantities of chitosan in composites permit the interaction with human albumin and improve the retention of fluid. The composites are slightly degraded by the lysozyme which facilitates an in vivo degradation control of bone substitutes. Modulus of elasticity is strongly dependent of the ratio chitosan/calcium phosphates and recommends the obtained biomimetic composites as promising materials for a prospective bone application.

Crosslinked hydrogels based on biological macromolecules with potential use in skin tissue engineering

Zero-length crosslinked hydrogels have been synthesized by covalent linking of three natural polymers (collagen, hyaluronic acid and sericin), in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The hydrogels have been investigated by FT-IR spectroscopy, microcalorimetry, in vitro swelling, enzymatic degradation, and in vitro cell viability studies. The obtained crosslinked hydrogels showed a macroporous structure, high swelling degree and in vitro enzymatic resistance compared to uncrosslinked collagen. The in vitro cell viability studies performed on normal human dermal fibroblasts assessed the sericin proliferation properties indicating a potential use of the hydrogels based on collagen, hyaluronic acid and sericin in skin tissue engineering.

Poly(Acrylic Acid)–Poly(Ethylene Glycol) Nanoparticles Designed for Ophthalmic Drug Delivery

Poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG), four-arm, amine-terminated particles with nanometer size and spherical shape were obtained by the polymers cross-linking, via activation with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride, in a w/o emulsion. The morphology and surface charge of the final particles are strongly dependent on the molar ratio of PAA-PEG and the PAA concentration. The physicochemical characteristics correlated with the drug-loading capacity, in vitro and ex vivo release kinetics of pilocarpine hydrochloride and biocompatibility results indicate that these nanoparticles exhibit the prerequisite behavior for use as carriers of ophthalmic drugs.

Biomimetic Composites Based on Calcium Phosphates and Chitosan - Hyaluronic Acid with Potential Application in Bone Tissue Engineering

Composites based on calcium phosphates (CP) and mixtures of biopolymers (chitosan and hyaluronic acid) have been prepared by a biomimetic co-precipitation method and tested as scaffolds for bone tissue engineering. The biomimetic strategy is inspired by natural mineralization processes, where the synthesized minerals are usually combined with proteins, polysaccharides or other mineral forms to form composite, in physiological conditions of temperature and pH. Fourier transformed infrared spectroscopy, scanning electron microscopy, X-ray diffraction and XPS analyses confirmed the porous morphology of the scaffolds and formation of various forms of calcium phosphates with amorphous nature. The in vitro degradation studies showed a slow degradation process for CP-biopolymers composites and limited swelling in simulated body fluids. The scaffolds compositions have no negative effect on osteoblasts cell, emphasizing a good biocompatibility.

The preparation, characterization and properties of catalase immobilized on crosslinked gellan

In the present paper, the reaction of chemical immobilization of catalase on a crosslinked macromolecular carrier of a polysaccharide structure (gellan) is studied. The influence of some reaction parameters (enzyme/carrier, activator/carrier ratios, duration) on the activity of enzymatic products is analyzed. The kinetics of the biocatalytic process, stability under different pH and temperature conditions, and the inhibitors effect were studied for the immobilized enzymes.

Crosslinked Networks Based on Polysaccharides and Collagen for Pilocarpine Sustained Release

The paper presents the experimental studies regarding synthesis and characterization of hydrogels based on gellan (Gel)/chitosan (CS) and collagen (Col), obtained by crosslinking with glutaraldehyde (GLA). The influence of the polysaccharide content and GLA ratio on the final composition and swelling characteristics was evaluated. Hydrogels swelling analysis, in distilled water and phosphate buffer (PBS, pH 7.2) has shown higher swelling degrees at increased concentration of polysaccharide into hydrogels. In vitro release of pilocarpine has demonstrated the possibility to use gellan-collagen and chitosan-collagen hydrogels as ophthalmic drug delivery matrix.

pH-Responsive 2-hydroxyethyl methacrylate/citraconic anhydride–modified collagen hydrogels as ciprofloxacin carriers for wound dressings

pH-Sensitive hydrogels of 2-hydroxyethyl methacrylate/citraconic anhydride–modified collagen were obtained by free radical copolymerization/crosslinking in the presence of ammonium persulfate/N,N,N′,N′-tetramethylethylenediamine redox initiator system. Their pH-responsiveness was demonstrated by swelling behavior and ciprofloxacin release tests. Both unloaded and loaded hydrogels were characterized by Fourier transform infrared, scanning electron microscopy, and biocompatibility tests. The enzymatic degradation in the presence of Clostridium histolyticum mainly depends on initiator content. In vivo biocompatibility tests involving intraperitoneal hydrogels’ implantation in rats following the analysis by the granuloma test, leukocyte formula, immune parameters, and hepatic transaminases demonstrated their non-toxicity and biocompatibility with living tissues. The in vitro antimicrobial activity, in vivo biocompatibility, and in vitro biodegradability tests attest the possibility to use these new polymeric hydrogels with tailored properties as matrices for bioactive products in medical and pharmaceutical applications as wound care and targeting drug delivery systems. The ciprofloxacin release studies proved their potential as materials for wound dressings.

Functionalized magnetic nanoparticles: Synthesis, characterization, catalytic application and assessment of toxicity

Cost-effective water cleaning approaches using improved treatment technologies, for instance based on catalytic processes with high activity catalysts, are urgently needed. The aim of our study was to synthesize efficient Fenton-like photo-catalysts for rapid degradation of persistent organic micropollutants in aqueous medium. Iron-based nanomaterials were chemically synthesized through simple procedures by immobilization of either iron(II) oxalate (FeO) or iron(III) citrate (FeC) on magnetite (M) nanoparticles stabilized with polyethylene glycol (PEG). Various investigation techniques were performed in order to characterize the freshly prepared catalysts. By applying advanced oxidation processes, the effect of catalyst dosage, hydrogen peroxide concentration and UV-A light exposure were examined for Bisphenol A (BPA) conversion, at laboratory scale, in mild conditions. The obtained results revealed that BPA degradation was rapidly enhanced in the presence of low-concentration H2O2, as well as under UV-A light, and is highly dependent on the surface characteristics of the catalyst. Complete photo-degradation of BPA was achieved over the M/PEG/FeO catalyst in less than 15 minutes. Based on the catalytic performance, a hierarchy of the tested catalysts was established: M/PEG/FeO > M/PEG/FeC > M/PEG. The results of cytotoxicity assay using MCF-7 cells indicated that the aqueous samples after treatment are less cytotoxic.

Medical Bioengineering Education in Iasi, Romania

Besides medical and pharmacy specialists, the engineering branch has a main role in modern health care, characterized by high medical technology, powerful software programs for data analysis, and top management tools to increase efficiency of the health care system. Among many engineering specialties, bioengineers and biomedical engineers, even if somehow different, have a main common feature: the strong inter-, multi- and transdisciplinarity of their work. The paper analyses some characteristics of the specific education process in both fields, shows their sub-domains of activity, presents opportunities related to designing a career, presents specific aspects of 21 years of medical bioengineering education in Iasi city, Romania, and concludes that medical bioengineering and biomedical engineering belong to the top jobs, with a constant growths in demand.