Nita Tudorachi

Novel Environmentally Friendly Copolymers Carboxymethyl Starch Grafted Poly(Lactic Acid)

Modified natural polymers have been gaining increasing scientific interest for many years. In this study carboxymethyl starch (CMS) was grafted with L(+)-lactic acid (LA) in different molar ratios CMS/LA (1/36, 1/22 and 1/12), resulting carboxymethyl starch-g-poly(lactic acid) (CMS-g-PLA) copolymers. The grafting reaction was carried out by solution polycondensation procedure in toluene and stannous 2-ethyl hexanoate Sn(Oct)2 as catalyst was utilized. Poly(lactic acid) (PLA) was synthesized in the same conditions with the copolymers for comparative analyses of the physico-chemical and thermal properties. The copolymers and PLA were structurally and morphologically characterized by FT-IR, 1H-NMR spectroscopy, WAXD and SEM analyses, taking CMS as reference. The molecular weight of the copolymers, CMS and PLA were determined, using a dynamic light scattering technique. The thermal behavior of the products was studied by DSC and TG-DTG analyses. The CMS-g-PLA graft copolymers exhibited lower Tg and thermal stability than pure CMS.

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.

Design and synthesis of a new polymer network containing pendant spiroacetal moieties

The present work describes the synthesis, properties, and sensitive behavior of a set of copolymers based on itaconic anhydride with different molar ratios of 3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5] undecane prepared through radical polymerization process, in the presence of 2,2-azobisisobutyronitrile as initiator. The chemical structure of the prepared copolymers was confirmed by FTIR and 1H NMR. The macromolecular compounds were characterized from the viewpoint of their thermal stability. The sensitivity of the new structures was evaluated by determining the hydrodynamic radius in interdependence with environmental conditions, and rheological properties were studied in terms of shear rate and viscosity. The versatility and untapped potential of these stimuli-sensitive polymeric systems generated by both comonomers – network formation, biodegradability and biocompatibility, gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability, good films formers, acid pH sensitivity, the possibilities to modify the anhydride ring through suitably reactions – makes them promising agents for pharmaceutical delivery systems or support for bioactive compounds, among other applications.

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.

Studies on Diels–Alder thermoresponsive networks based on ether–urethane bismaleimide functionalized poly(vinyl alcohol)

Thermoreversible networks obtained by the Diels–Alder cycloaddition reaction of poly(vinyl furfural) with urethane bismaleimides containing polyether chain were synthesized. The formation of the networks was confirmed by attenuated total reflectance in conjunction with Fourier transform infrared spectroscopy (ATR–FTIR). The materials thermal properties were investigated using differential scanning calorimetry (DSC) and a coupling of dynamic thermogravimetry with Fourier transform infrared spectroscopy and mass spectrometry (TG–FTIR–MS) for pyrolysis behaviour under nitrogen atmosphere. A thermal decomposition mechanism of the networks and poly(vinyl furfural) was discussed via evolved gas analysis. The thermoreversibility of the networks was demonstrated by the presence of the endothermic peak characteristic to the retrodienic process on the DSC heating curves and also the appearance of the exothermic peak, due to the dienic process, on the DSC cooling curve. The dynamic contact angle and free surface energy values of the networks were determined. Measures of the heterogeneity and roughness of the surfaces suggested that the surfaces of the networks’ films are more homogenous than the initial poly(vinyl furfural) surface. Dynamic water vapour sorption studies were conducted.

Thermal behavior of epoxy resin cured with aromatic dicarboxylic acids

The curing kinetics and thermal properties of diglycidyl ether of bisphenol A crosslinked with two aromatic diacids were studied using non-isothermal differential scanning calorimetry and simultaneous TG/FTIR/MS analysis. In the crosslinking of the epoxy resins with anhydrides, there is an intermediate stage resulting acids, while the direct use of acids eliminate this phase. The kinetic parameters of the curing reactions were calculated using Kissinger, Flynn–Wall–Ozawa methods and also the multivariate nonlinear regression method included in Netzsch Thermokinetics software. The kinetic parameters and the thermal degradation mechanisms for the crosslinked resins were determined using the same software. The thermal degradation processes occurred in three steps, depending on the chemical structure of the samples. The thermal lifetime of the crosslinked resins was also calculated.

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.

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

ABSTRACT 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.

Tailorable polyelectrolyte protein complex based on poly(aspartic acid) and bovine serum albumin

Abstract Protein–polyelectrolyte complexes (PPC) are playing an important role in a variety of chemical and biological processes, such as protein separation, enzyme stabilization, and polymer drug delivery. The present investigation is focused on evaluation of the PPC formation between a synthetic polypeptide (poly(aspartic acid) – PAS) and a natural protein (bovine serum albumin – BSA). The PPC obtained from PAS and BSA in different ratio was investigated by corroboration of various techniques of characterization as: spectroscopy, microscopy, thermogravimetric analysis, dynamic light scattering (DLS), and zeta potential determination, measurements which were performed in static and/or dynamic conditions. The static contact angle of the sample films was also determined in order to evaluate the changes brought upon surface free energy of the prepared PPCs in interdependence with the complexes composition. The critical conditions for complex formation in BSA–polyelectrolyte systems were underlined. The phenomenon was better evidenced in case of a ratio of 1/1 wt between the two polymers, both in static and/or dynamic conditions.

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.