Exploring the Antioxidant Potency of New Naphthalene-Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations.

Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2-acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment with both nitrogen and carbon nucleophiles, and yielded diverse heterocyclic scaffolds such as pyrazoline, thiazole, pyrimidine, pyran, and pyridine derivatives. The pyrazoline aldehyde derivative 7 was further derivatized to produce the hydrazide-hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which was exploited to synthesize derivatives of 2-oxo-2H-chromene-3-carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, and 3-(4-nitrophenyl)acrylohydrazide 16. All the newly synthesized compounds were characterized by melting point, elemental analysis, as well as FT-IR, 1 H-NMR and mass spectroscopy. Furthermore, these heterocyclic derivatives were screened for their antioxidant capacities using the DPPH radical assay. The results showed that compounds 5 and 10 are the most potent antioxidants with IC50 values 178, 177(µM), respectively. comparable to that of ascorbic acid which has IC50 value 148. Meanwhile, compounds 2, 12, 13, 14, 15, and 16 exhibited moderate antioxidant activities with IC50 values ranged from 266 to 291(µM). Thus, these heterocycles could emerge as promising antioxidant drugs for the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 5, 10, and ascorbic acid inside the active pocket of Human Peroxiredoxin 5 (1HD2). DFT calculations and global descriptors were calculated for the most potent compounds to correlate the relation between chemical structure and reactivity.

Polyethylene oxide-polyacrylic acid-folic acid (PEO-PAAc) nanogel as a 99m Tc targeting receptor for cancer diagnostic imaging.

Nanoparticles are frequently used as targeting delivery systems for therapeutic and diagnostic radiopharmaceuticals. Polyethylene oxide-polyacrylic acid (PEO-PAAc) nanogel was prepared via γ-radiation-induced polymerization. Variable factors affecting nanoparticles size were investigated. The nanogel was radiolabeled with the imaging radioisotope 99m Tc and finally conjugated with folic acid to target folate receptor actively. PEO-PAAc-folic acid gel was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). Biodistribution was studied in normal mice and solid tumor-bearing mice via intravenous and intratumor injections of the radiolabeled PEO-PAAc-folic acid nanogel. Results of biodistribution showed high selective uptake of the prepared complex in tumor muscle compared with normal muscle for both intravenous and intratumor injections. The T/NT ratio was found to be 6.186 and 294.5 for intravenous and intratumor injections, respectively. Consequently, 99m Tc-PEO-PAAc-folic acid complex could be a promising agent for cancer diagnostic imaging.

Nanoscale poly(acrylic acid)-based hydrogels prepared via a green single-step approach for application as low-viscosity biomimetic fluid tears.

The present work reports a nanotechnology strategy to prepare a low-viscosity poly(acrylic acid) (PAAc)-based tear substitute with enhanced efficacy and compliance. Specifically, nanogels composed of PAAc and polyvinylpyrrolidone (PVP) were prepared by adapting an ionizing radiation method. For this purpose, different aqueous systems: PVP/PAAc nanoparticulate complexes, PVP/acrylic acid (AAc), N-vinylpyrrolidone (N-VP)/PAAc, and N-VP/AAc were exposed to gamma rays. The dynamic light scattering technique showed that stable nanogels are only produced in a relatively high yield from the PVP/AAc system. Nanogel formation was driven by the hydrogen-bonding complexation between PVP and PAAc (formed in situ) as well as the radiation-induced cross-linking. Transparency, viscosity and mucoadhesiveness of emerged nanogels were optimized by controlling the feed composition and irradiation dose. Furthermore, neutralized nanogels were topically applied in a dry eye model and compared with a PAAc-based commercial tear substitute, namely Vidisic® Gel. The results of Schirmer's test and tear break-up time demonstrated that nanogels prepared from AAc-rich feed solutions at 20 kGy enhanced markedly the dry eye conditions. The histopathological analysis also ensured the competence of PAAc-rich nanogels to completely return the corneal epithelium to its normal state.

Description of D-glucosamine immobilization kinetics onto poly(lactic acid) surface via a multistep physicochemical approach for preparation of novel active biomaterials.

Poly(lactic acid) (PLA) has shown much success in the preparation of tissue engineering scaffolds as it can be fabricated with a tailored architecture. However, the PLA surface has drawbacks including the lack of biofunctional motifs which are essential for high affinity to biological cells. Therefore, this study describes a multistep physicochemical approach for the immobilization of d-glucosamine (GlcN), a naturally occurring monosaccharide having many biological functions, on the PLA surface aiming at enhancing the cell proliferation activity. In this approach, poly(acrylic acid) (PAAc) spacer arms are first introduced into the PLA surface via plasma post-irradiation grafting technique. Then, covalent coupling or physical adsorption of GlcN with/on the PAAc spacer is carried out. Factors affecting the grafting yield are controlled to produce a suitable spacer for bioimmobilization. X-ray photon spectroscopic (XPS) analyses confirm the immobilization of GlcN on the PLA surface. The XPS results reveal also that increasing the yield of grafted PAAc spacer on the PLA surface increases the amount of covalently immobilized GlcN, but actually inhibits the immobilization process using the physical adsorption method. Contact angle measurements and atomic force microscopy (AFM) show a substantial increase of surface energy and roughness of PLA surface, respectively, upon the multistep modification procedure. The cytocompatibility of the modified surfaces is assessed using a mouse embryonic fibroblast (MEF) cell line. Observation from the cell culture basically demonstrates the potential of GlcN immobilization in improving the cytocompatibility of the PLA surface. Moreover, the covalent immobilization of GlcN seems to produce more cytocompatible surfaces if compared with the physical adsorption method. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3176-3188, 2017.

Developing a biomaterial interface based on poly(lactic acid) via plasma-assisted covalent anchorage of d-glucosamine and its potential for tissue regeneration.

The aim of this study was to develop the potential tissue engineering applications of d-glucosamine (GlcN) immobilized onto the surface of a biodegradable matrix in order to induce a desired biological effect at biointerfaces. Thus, for sample preparation we used a novel multistep physicochemical approach. In the first step the poly(lactic acid) (PLA) films were exposed to a low pressure plasma in air atmosphere, followed by radical graft copolymerization with acrylic acid to yield a carboxyl-functionalized spacer layer on the PLA surface. The carboxyl groups were then coupled to GlcN molecules via the carbodiimide chemistry. The developed surfaces were characterized by X-ray Photoelectron Spectroscopy (XPS), Contact angle measurements and Atomic Force Microscopy (AFM). A preliminary study on the proliferation of fibroblasts on the developed surfaces was performed using the NIH/3T3 cell line.

Developing the potential ophthalmic applications of pilocarpine entrapped into polyvinylpyrrolidone-poly(acrylic acid) nanogel dispersions prepared by γ radiation.

The aim of this study was to improve the stability and bioavailability of pilocarpine in order to maintain an adequate concentration of the pilocarpine at the site of action for prolonged period of time. Thus, pH-sensitive polyvinylpyrrolidone-poly(acrylic acid) (PVP/PAAc) nanogels prepared by γ radiation-induced polymerization of acrylic acid (AAc) in an aqueous solution of polyvinylpyrrolidone (PVP) as a template polymer were used to encapsulate pilocarpine. Factors affecting size and encapsulation efficiency were optimized to obtain nanogel suitable for entrapping drug efficiently. The PVP/PAAc nanogel particles were characterized by dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM), and their size can be controlled by the feed composition and concentration as well as the irradiation dose. Pilocarpine was loaded into the nanogel particles through electrostatic interactions where the AAc-rich nanogels exhibited the highest loading efficiency. The transmittance, mucoadhesion, and rheological characteristics of the nanogel particles were studied to evaluate their ocular applicability. The in vitro release study conducted in simulated tear fluid showed a relatively long sustained release of pilocarpine from the prepared PVP/PAAc nanogel particles if compared with pilocarpine in solution.