An Accessible Method to Improve the Stability and Reusability of Porcine Pancreatic α-Amylase via Immobilization in Gellan-Based Hydrogel Particles Obtained by Ionic Cross-Linking with Mg2+ Ions.

Amylase is an enzyme used to hydrolyze starch in order to obtain different products that are mainly used in the food industry. The results reported in this article refer to the immobilization of α-amylase in gellan hydrogel particles ionically cross-linked with Mg2+ ions. The obtained hydrogel particles were characterized physicochemically and morphologically. Their enzymatic activity was tested using starch as a substrate in several hydrolytic cycles. The results showed that the properties of the particles are influenced by the degree of cross-linking and the amount of immobilized α-amylase enzyme. The temperature and pH at which the immobilized enzyme activity is maximum were T = 60 °C and pH = 5.6. The enzymatic activity and affinity of the enzyme to the substrate depend on the particle type, and this decreases for particles with a higher cross-linking degree owing to the slow diffusion of the enzyme molecules inside the polymer's network. By immobilization, α-amylase is protected from environmental factors, and the obtained particles can be quickly recovered from the hydrolysis medium, thus being able to be reused in repeated hydrolytic cycles (at least 11 cycles) without a substantial decrease in enzymatic activity. Moreover, α-amylase immobilized in gellan particles can be reactivated via treatment with a more acidic medium.

Photoluminescent Polymer Aerogels with R, G and B Emission.

In this work, three new polymer aerogels based on 2-hydroxy ethyl methacrylate (HEMA) complexes with Eu(III), Tb(III) and La(III) are prepared and investigated. The polymer aerogels present strong photoluminescence with emissions located in the red, green and blue regions of the visible spectrum. Depending on the water content used during the preparation path, the consistency of the photoluminescent aerogels varies from rigid, regularly shaped monoliths to a flexible, fibrous material with very low density. The morpho-structural investigation was performed by FT-IR, XPS and SEM. Thermal behavior was also evaluated, while steady-state fluorescence spectroscopy, absolute PLQY and lifetime were used for the investigation of their luminescent properties. The impressive photoluminescent emission located in the red, green and blue areas of the visible spectrum is preserved irrespective of the selected porosity. Their photo-emissive properties, tunable porosity and the convenience of the preparation path could be some arguments for applications as photonic conversion mediums in special-purpose optoelectronic devices or sensors.

Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma.

Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core-shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure.

The Benefits of Smart Nanoparticles in Dental Applications.

Dentistry, as a branch of medicine, has undergone continuous evolution over time. The scientific world has focused its attention on the development of new methods and materials with improved properties that meet the needs of patients. For this purpose, the replacement of so-called "passive" dental materials that do not interact with the oral environment with "smart/intelligent" materials that have the capability to change their shape, color, or size in response to an externally stimulus, such as the temperature, pH, light, moisture, stress, electric or magnetic fields, and chemical compounds, has received much attention in recent years. A strong trend in dental applications is to apply nanotechnology and smart nanomaterials such as nanoclays, nanofibers, nanocomposites, nanobubbles, nanocapsules, solid-lipid nanoparticles, nanospheres, metallic nanoparticles, nanotubes, and nanocrystals. Among the nanomaterials, the smart nanoparticles present several advantages compared to other materials, creating the possibility to use them in various dental applications, including preventive dentistry, endodontics, restoration, and periodontal diseases. This review is focused on the recent developments and dental applications (drug delivery systems and restoration materials) of smart nanoparticles.

Polysaccharides-Based Complex Particles' Protective Role on the Stability and Bioactivity of Immobilized Curcumin.

The curcumin degradation represents a significant limitation for its applications. The stability of free curcumin (FC) and immobilized curcumin in complex particles (ComPs) based on different polysaccharides was studied under the action of several factors. Ultraviolet-visible (UV-VIS) and Fourier-transform infrared (FTIR) spectroscopy proved the FC photodegradation and its role as a metal chelator: 82% of FC and between 26% and 39.79% of curcumin within the ComPs degraded after exposure for 28 days to natural light. The degradation half-life (t1/2) decreases for FC when the pH increases, from 6.8 h at pH = 3 to 2.1 h at pH = 9. For curcumin extracted from ComPs, t1/2 was constant (between 10 and 13 h) and depended on the sample's composition. The total phenol (TPC) and total flavonoids (TFC) content values increased by 16% and 13%, respectively, for FC exposed to ultraviolet light at λ = 365 nm (UVA), whereas no significant change was observed for immobilized curcumin. Antioxidant activity expressed by IC50 (µmoles/mL) for FC exposed to UVA decreased by 29%, but curcumin within ComPs was not affected by the UVA. The bovine serum albumin (BSA) adsorption efficiency on the ComPs surface depends on the pH value and the cross-linking degree. ComPs have a protective role for the immobilized curcumin.

Optimized Synthesis of New Thiosemicarbazide Derivatives with Tuberculostatic Activity.

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives' applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and 1H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against Mycobacterium tuberculosis.

Synthesis of 1-(2-Fluorophenyl)pyrazoles by 1,3-Dipolar Cycloaddition of the Corresponding Sydnones.

3-Arylsydnones bearing fluorine and bromine atoms on the benzene ring were synthesized from N-nitroso-2-fluorophenylglycines and characterized by NMR spectroscopy. These were employed further in synthesis of the corresponding 1-(2-fluorophenyl)pyrazoles by 1,3-dipolar cycloaddition reaction with dimethyl acetylenedicarboxylate (DMAD) as activated dipolarophile. The sydnones as reaction intermediates were characterized by single crystal X-ray diffraction analysis showing interesting features such as halogen bonding as an important interaction in modeling the crystal structure.

Polysaccharide-Based Drug Delivery Systems for the Treatment of Periodontitis.

Periodontal diseases are worldwide health problems that negatively affect the lifestyle of many people. The long-term effect of the classical treatments, including the mechanical removal of bacterial plaque, is not effective enough, causing the scientific world to find other alternatives. Polymer-drug systems, which have different forms of presentation, chosen depending on the nature of the disease, the mode of administration, the type of polymer used, etc., have become very promising. Hydrogels, for example (in the form of films, micro-/nanoparticles, implants, inserts, etc.), contain the drug included, encapsulated, or adsorbed on the surface. Biologically active compounds can also be associated directly with the polymer chains by covalent or ionic binding (polymer-drug conjugates). Not just any polymer can be used as a support for drug combination due to the constraints imposed by the fact that the system works inside the body. Biopolymers, especially polysaccharides and their derivatives and to a lesser extent proteins, are preferred for this purpose. This paper aims to review in detail the biopolymer-drug systems that have emerged in the last decade as alternatives to the classical treatment of periodontal disease.

Immobilization and Release Studies of Triazole Derivatives from Grafted Copolymer Based on Gellan-Carrying Betaine Units.

New polymer-bioactive compound systems were obtained by immobilization of triazole derivatives onto grafted copolymers and grafted copolymers carrying betaine units based on gellan and N-vinylimidazole. For preparation of bioactive compound, two new types of heterocyclic thio-derivatives with different substituents were combined in a single molecule to increase the selectivity of the biological action. The 5-aryl-amino-1,3,4 thiadiazole and 5-mercapto-1,2,4-triazole derivatives, each containing 2-mercapto-benzoxazole nucleus, were prepared by an intramolecular cyclization of thiosemicarbazides-1,4 disubstituted in acidic and basic medium. The structures of the new bioactive compounds were confirmed by elemental and spectral analysis (FT-IR and 1H-NMR). The antimicrobial activity of 1,3,4 thiadiazoles and 1,2,4 triazoles was tested on gram-positive and gram-negative bacteria. The triazole compound was chosen to be immobilized onto polymeric particles by adsorption. The Langmuir, Freundlich, and Dubinin-Radushkevich adsorption isotherm were used to describe the adsorption equilibrium. Also, the pseudo-first and pseudo-second models were used to elucidate the adsorption mechanism of triazole onto grafted copolymer based on N-vinylimidazole and gellan (PG copolymer) and grafted copolymers carrying betaine units (PGB1 copolymer). In vitro release studies have shown that the release mechanism of triazole from PG and PGB1 copolymers is characteristic of an anomalous transport mechanism.

Hydrogel Films Based on Chitosan and Oxidized Carboxymethylcellulose Optimized for the Controlled Release of Curcumin with Applications in Treating Dermatological Conditions.

Cross-linked chitosan (CS) films with aldehyde groups obtained by oxidation of carboxymethyl cellulose (CMC) with NaIO4 were prepared using different molar ratios between the CHO groups from oxidized carboxymethyl cellulose (CMCOx) and NH2 groups from CS (from 0.25:1 to 2:1). Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy demonstrated the aldehyde groups' presence in the CMCOx. The maximum oxidation degree was 22.9%. In the hydrogel, the amino groups' conversion index value increased when the -CHO/-NH2 molar ratio, cross-linking temperature, and time increased, while the swelling degree values decreased. The hydrogel films were characterized by scanning electron microscopy (SEM) and FTIR analysis. The curcumin encapsulation efficiency decreases from 56.74% to 16.88% when the cross-linking degree increases. The immobilized curcumin release efficiency (REf%) and skin membrane permeability were evaluated in vitro in two different pH solutions using a Franz diffusion cell, and it was found to decrease when the molar ratio -CH=O/NH2 increases. The curcumin REf% in the receptor compartment was higher at pH = 7.4 (18%- for the sample with a molar ratio of 0.25:1) than at pH = 5.5 (16.5%). The curcumin absorption in the skin membrane at pH = 5.5 (47%) was more intense than at pH = 7.4 (8.6%). The curcumin-loaded films' antioxidant activity was improved due to the CS presence.

A Theoretical Model for Release Dynamics of an Antifungal Agent Covalently Bonded to the Chitosan.

The aim of the study was to create a mathematical model useful for monitoring the release of bioactive aldehydes covalently bonded to the chitosan by reversible imine linkage, considered as a polymer-drug system. For this purpose, two hydrogels were prepared by the acid condensation reaction of chitosan with the antifungal 2-formyl-phenyl-boronic acid and their particularities; influencing the release of the antifungal aldehyde by shifting the imination equilibrium to the reagents was considered, i.e., the supramolecular nature of the hydrogels was highlighted by polarized light microscopy, while scanning electron microscopy showed their microporous morphology. Furthermore, the in vitro fungicidal activity was investigated on two fungal strains and the in vitro release curves of the antifungal aldehyde triggered by the pH stimulus were drawn. The theoretical model was developed starting from the hypothesis that the imine-chitosan system, both structurally and functionally, can be assimilated, from a mathematical point of view, with a multifractal object, and its dynamics were analyzed in the framework of the Scale Relativity Theory. Thus, through Riccati-type gauges, two synchronous dynamics, one in the scale space, associated with the fungicidal activity, and the other in the usual space, associated with the antifungal aldehyde release, become operational. Their synchronicity, reducible to the isomorphism of two SL(2R)-type groups, implies, by means of its joint invariant functions, bioactive aldehyde compound release dynamics in the form of "kink-antikink pairs" dynamics of a multifractal type. Finally, the theoretical model was validated through the experimental data.

Antitumoral Drug: Loaded Hybrid Nanocapsules Based on Chitosan with Potential Effects in Breast Cancer Therapy.

Cancer remains one of the world's most devastating diseases and is responsible for more than 20% of all deaths. It is defined as uncontrolled proliferation of cells and spreads rapidly to healthy tissue. Controlled drug delivery systems offers great opportunities for the development of new non-invasive strategies for the treatment of cancers. The main advantage of these systems is their capacity to accumulate in tumors via enhanced permeability and retention effects. In the present study, an innovative hybrid drug delivery system based on nanocapsules obtained from the interfacial condensation between chitosan and poly(N-vinyl pyrrolidone-alt-itaconic anhydride) and containing both magnetic nanoparticles and an antitumoral drug was developed in order to improve the efficiency of the antitumoral treatment. Using dynamic light scattering, it was observed that the mean diameter of these hybrid nanocapsules was in the range of 43 to 142 nm. SEM confirmed their nanometric size and their well-defined spherical shape. These nanocapsules allowed the encapsulation of an increased amount of 5-fluorouracil and provided controlled drug release. In vitro studies have revealed that these drug-loaded hybrid nanocapsules were able to induce a cytostatic effect on breast carcinoma MCF-7 cell lines (Human Caucasian breast adenocarcinoma - HTB-22) comparable to that of the free drug.

Effects and Characterization of Some Topical Ointments Based on Vegetal Extracts on Incision, Excision, and Thermal Wound Models.

The present paper aims to formulate and characterize four phytotherapeutic ointments based on Hippophae fructus, Calendulae flos, Bardanae folium, and Millefolii herba, which are included in a novel ointment base. In order to investigate the healing properties of the ointments, in vivo experimental wound models of linear incision, circular excision, and thermal burn were performed on Wistar rats. Topical treatment was performed daily for 21 days. Determination of the wound contraction rate (WCR), the period of reepithelization, and histopathological examination were achieved. Additionally, for the tested ointments, oscillatory and rotational rheological tests were carried out, and for the extracts, HPLC analysis was performed. The results demonstrate that the tested novel ointments are safe for use and the most effective ointment proved to be the one based on Arctium lappa, followed by that of Calendulae flos.

New Grafted Copolymers Carrying Betaine Units Based on Gellan and N-Vinylimidazole as Precursors for Design of Drug Delivery Systems.

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of N-vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/N,N,N',N' tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: ci = 0.08 mol/L, cm = 0.8 mol/L, cp = 8 g/L, tr = 4 h and T = 50 °C. The kinetics of the graft copolymerization of N-vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, 1H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.

Polyglobalide-Based Porous Networks Containing Poly(ethylene glycol) Structures Prepared by Photoinitiated Thiol-Ene Coupling.

The high interest in polymers from natural resources prompted us to investigate the use of enzymatically synthesized polyglobalide (PGL) in the preparation of polymer networks with potential applications as biomaterials for drug delivery devices. Polymer networks were obtained under mild conditions by photoinitiated thiol-ene coupling between PGL and a poly(ethylene glycol- co-thiomalate) (PEG-SH) copolymer obtained by polycondensation. The obtained polymer networks were thoroughly characterized by Raman spectroscopy, scanning electron microscopy, titration of thiol groups and elemental analysis. Our study took into consideration the synthesis parameters for the polymer networks, such as the total polymer concentration and the SH/C=C functionality molar ratio. Swelling in both THF and water was assessed, and the potential of the materials for drug delivery was determined. The scanning electron microscopy images showed that the prepared polymer networks may have different morphologies ranging from homogeneous polymer materials to macroporous structures. Additionally, the prepared materials were found to be suitable from a cytotoxicity point of view, enabling their application as biomaterials for drug delivery devices.

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.

Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration.

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

Microparticulated systems based on chitosan and poly(vinyl alcohol) with potential ophthalmic applications.

Spherical microparticles for encapsulation of drugs for the treatment of diseases, with a diameter ranging between 2 and 4 µm, were obtained by double crosslinking (ionic and covalent) of chitosan and poly(vinyl alcohol) blend in a water-in-oil emulsion. Microparticles characterisation was carried out in terms of structural, morphological and swelling properties in aqueous media. The presence of chitosan in particles composition confers them a pH-sensitive character. Toxicity and hemocompatibility tests prove the biocompatible character of microparticles. The pilocarpine loading capacity is high as well as the release efficiency which increases up to 72 and 82% after 6 h. The obtained results recommend the microparticles as sustained release drug carriers for the treatment of eye diseases.

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively.

The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their corresponding cycloimmonium bromides. In the case of 4-(3-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur as expected at the pyridine nitrogen atom leading to pyridinium bromides and consequently to new indolizines via the corresponding pyridinium N-ylides. However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new indolizines were structurally characterized through NMR spectroscopy. The X-ray structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine, are also reported.

Effect of apitherapy formulations against carbon tetrachloride-induced toxicity in Wistar rats after three weeks of treatment.

The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels) and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution). Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals.