Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer

(1) Background: Pretreatment by Rad51-inhibitory substances such as gemcitabine followed by arterial chemotherapy using antineoplastic agents causing DNA crosslink might be more beneficial for patients with locally advanced pancreatic cancers than conventional treatments. The efficacy of arterial administration of DNA crosslinking agents with pretreatment of intravenous low-dose gemcitabine for patients with unresectable locally advanced or metastatic pancreatic cancer (LAPC or MPC) is evaluated. (2) Methods: A single-arm, single-center, institutional review board-approved prospective study was conducted between 2005 and 2015. Forty-five patients (23 LAPC, 22 MPC) were included. Patients received a weekly low dose of gemcitabine intravenously for three weeks followed by arterial administration of mitomycin C and epirubicin hydrochloride at tumor-supplying arteries on the fifth or sixth week. This treatment course was repeated at 1.5-to-2-month intervals. Overall survival (OS), local progression-free survival (LPFS), and therapeutic response were evaluated. LAPC or MPC were divided according to treatment compliance, excellent or poor (1 or 2), to subgroups L1, L2, M1, and M2. (3) Results: OS of LAPC and MPC were 23 months and 13 months, respectively. The OS of LAPC with excellent treatment compliance (subgroup L1, 10 patients) was 33 months with 31 months of LPFS, and four patients (40%) had a complete response (CR). The OS of the L1 subgroup was significantly longer than those of other subgroups L2, M1, and M2, which were 17 months, 17 months, and 8 months, respectively. As Grade 3 adverse effects, severe bone marrow suppression, interstitial pneumonitis, and hemolytic uremic syndrome were observed in six (13.0%), three (6.5%), and three (6.5%) patients, respectively. (4) Conclusions: Arterial DNA crosslinking with the systemic restraint of homologous recombination repair can be a new treatment option for LAPC.

ELASTOMERS WITH A HIGH CONTENT OF MODIFIED CARBOXYMETHYLCELLULOSE

The use of lactam-containing complex salts (LCS) with the functions of dispersants, apparatuses and crosslinking agents made it possible to obtain elastomers with a high (at least 300 wt.% per 100 wt.h. of rubber), containing modified carboxymethyl cellulose for the cuff of a packer device capable of performing the necessary shut-off functions in contact with highly concentrated, at least 25% aqueous solutions of mineral salts - NaCl and CaCl2. The achieved effect is expressed in the ability of LCS to disperse water-swelling polymers (GNP), to have an appreting effect on GNP particles, thereby preventing their agglomeration, as well as to create additional chemisorption bonds in the rubber matrix. As a result, a developed network of interface boundaries is obtained, which contributes to the rapid penetration of aqueous solutions of mineral salts into the array of elastomeric composition.

Composite Nanocellulose Fibers-Based Hydrogels Loading Clindamycin HCl with Ca2+ and Citric Acid as Crosslinking Agents for Pharmaceutical Applications

Biocomposite hydrogels based on nanocellulose fibers (CNFs), low methoxy pectin (LMP), and sodium alginate (SA) were fabricated via the chemical crosslinking technique. The selected CNFs-based hydrogels were loaded with clindamycin hydrochloride (CM), an effective antibiotic as a model drug. The properties of the selected CNFs-based hydrogels loaded CM were characterized. The results showed that CNFs-based hydrogels composed of CNFs/LMP/SA at 1:1:1 and 2:0.5:0.5 mass ratios exhibited high drug content, suitable gel content, and high maximum swelling degree. In vitro assessment of cell viability revealed that the CM-incorporated composite CNFs-based hydrogels using calcium ion and citric acid as crosslinking agents exhibited high cytocompatibility with human keratinocytes cells. In vitro drug release experiment showed the prolonged release of CM and the hydrogel which has a greater CNFs portion (C2P0.5A0.5/Ca + Ci/CM) demonstrated lower drug release than the hydrogel having a lesser CNFs portion (C1P1A1/Ca + Ci/CM). The proportion of hydrophilic materials which were low methoxy pectin and sodium alginate in the matrix system influences drug release. In conclusion, biocomposite CNFs-based hydrogels composed of CNFs/LMP/SA at 1:1:1 and 2:0.5:0.5 mass ratios, loading CM with calcium ion and citric acid as crosslinking agents were successfully developed for the first time, suggesting their potential for pharmaceutical applications, such as a drug delivery system for healing infected wounds.

Technological features of reactive dynamic extrusion of nanocomposites based on polyolefins, aluminum and technical carbon

The effect of the concentration of aluminum powder and technical carbon nanoparticles on the main physical and mechanical properties of nanocomposites based on high density polyethylene, low density polyethylene and an ethylene-hexene copolymer is considered. The optimal technological parameters of the reaction extrusion of nanocomposites vulcanized with sulfur and dicumyl peroxide have been determined. The influence of the type of polyolefin, fillers and crosslinking agents on the formation of isotropic nanocomposites during the production of sheet products has been investigated.

On the Mechanism and Kinetics of Synthesizing Polymer Nanogels by Ionizing Radiation-Induced Intramolecular Crosslinking of Macromolecules

Nanogels—internally crosslinked macromolecules—have a growing palette of potential applications, including as drug, gene or radioisotope nanocarriers and as in vivo signaling molecules in modern diagnostics and therapy. This has triggered considerable interest in developing new methods for their synthesis. The procedure based on intramolecular crosslinking of polymer radicals generated by pulses of ionizing radiation has many advantages. The substrates needed are usually simple biocompatible polymers and water. This eliminates the use of monomers, chemical crosslinking agents, initiators, surfactants, etc., thus limiting potential problems with the biocompatibility of products. This review summarizes the basics of this method, providing background information on relevant aspects of polymer solution thermodynamics, radiolysis of aqueous solutions, generation and reactions of polymer radicals, and the non-trivial kinetics and mechanism of crosslinking, focusing on the main factors influencing the outcomes of the radiation synthesis of nanogels: molecular weight of the starting polymer, its concentration, irradiation mode, absorbed dose of ionizing radiation and temperature. The most important techniques used to perform the synthesis, to study the kinetics and mechanism of the involved reactions, and to assess the physicochemical properties of the formed nanogels are presented. Two select important cases, the synthesis of nanogels based on polyvinylpyrrolidone (PVP) and/or poly(acrylic acid) (PAA), are discussed in more detail. Examples of recent application studies on radiation-synthesized PVP and PAA nanogels in transporting drugs across the blood–brain barrier and as targeted radioisotope carriers in nanoradiotherapy are briefly described.

An Injectable Chitosan-Based Self-Healable Hydrogel System as An Antibacterial Wound Dressing

Due to their biodegradability and biocompatibility, chitosan-based hydrogels have great potential in regenerative medicine, with applications such as bacteriostasis, hemostasis, and wound healing. However, toxicity and high cost are problems that must be solved for chitosan-based hydrogel crosslinking agents such as formaldehyde, glutaraldehyde, and genipin. Therefore, we developed a biocompatible yet cost-effective chitosan-based hydrogel system as a candidate biomaterial to prevent infection during wound healing. The hydrogel was fabricated by crosslinking chitosan with dialdehyde chitosan (CTS–CHO) via dynamic Schiff-base reactions, resulting in a self-healable and injectable system. The rheological properties, degradation profile, and self-healable properties of the chitosan-based hydrogel were evaluated. The excellent antibacterial activity of the hydrogel was validated by a spread plate experiment. The use of Live/Dead assay on HEK 293 cells showed that the hydrogel exhibited excellent biocompatibility. The results demonstrate that the newly designed chitosan-based hydrogel is an excellent antibacterial wound dressing candidate with good biocompatibility.

An insight on 3D Bioink for fabricating porous materials for tissue engineering applications

Fabrication of biomaterials for Tissue Engineering application by bioprinting has gained enormous attention in the research field, owing to their rapid and reproducibility factor. Progress in organic based mesoporous particles is of great interest in order to accomplish in tissue engineering treatments. Recently, researchers are focusing on different 3D bioinks for attaining 3D matrices to accommodate the drugs and cells for biological efficacies. Bioprinting is a promising field of biomaterials and regenerative medicine for the next generation therapeutics. Different polymeric substances are being evaluated for their printablity based on their rheological and biological properties. Structural fidelity is stabilized by crosslinking methods and their adaptability to microenvironment is assessed using Invitro assays. External Factors such as concentration, temperature, medium and crosslinking agents are the critical determinants for the bionks to achieve the required functionality. Moreover, the choice base chemicals used for the formulation plays a vital role in the cell viability and proliferation that lead to specific tissue growth. The mechanical strength, elastic moduli to bear strength is anchored by the porous nature of the printed scaffolds. Therefore, the influence of porosity in the mechanical and biological strength adds an appropriate value to the printed biomaterial. The present review discusses about the significance of bioprinting technique and strategies employed for printability and to achieve porosity in the developed materials

Crosslinked Sodium Alginate as a Material for Nanolfiltration Protonic and Aprotonic Solvents

In this work, for the first time, salts of bivalent and trivalent metals were used as crosslinking agents for nanofiltration membranes based on sodium alginate. The developed membranes were investigated for chemical stability in protic and aprotic solvents, the dependence of the permeability of these solvents on their sorption into the membrane material was obtained. The separating properties of membranes based on sodium alginate crosslinked with metal cations were investigated. The retention coefficient of the model substance with a molecular weight of 626 g/mol, dissolved in ethanol, was 97%.