The study of double-network carboxymethyl chitosan/sodium alginate based cryogels for rapid hemostasis in noncompressible hemorrhage.

Developing an injectable hemostatic dressing with shape recovery and high blood absorption ratio for rapid hemostasis in noncompressible hemorrhage maintains a critical clinical challenge. Here, double-network cryogels based on carboxymethyl chitosan, sodium alginate, and methacrylated sodium alginate were prepared by covalent crosslinking and physical crosslinking, and named carboxymethyl chitosan/methacrylated sodium alginate (CM) cryogels. Covalent crosslinking was achieved by methacrylated sodium alginate in the freeze casting process, while physical crosslinking was realized by electrostatic interaction between the amino group of carboxymethyl chitosan and the carboxyl group of sodium alginate. CM cryogels exhibited large water swelling ratios (8167 ± 1062 %), fast blood absorption speed (2974 ± 669 % in 15 s), excellent compressive strength (over 160 kPa for CM100) and shape recovery performance. Compared with gauze and commercial gelatin sponge, better hemostatic capacities were demonstrated for CM cryogel with the minimum blood loss of 40.0 ± 8.9 mg and the lowest hemostasis time of 5.0 ± 2.0 s at hemostasis of rat liver. Made of natural polysaccharides with biocompatibility, hemocompatibility, and cytocompatibility, the CM cryogels exhibit shape recovery and high blood absorption rate, making them promising to be used as an injectable hemostatic dressing for rapid hemostasis in noncompressible hemorrhage.

Deep Eutectic Solvents Based on L-Arginine and 2-Hydroxypropyl-ß-Cyclodextrin for Drug Carrier and Penetration Enhancement.

By selecting L-arginine as the hydrogen bond acceptor (HBA) and 2-hydroxypropyl-ß-cyclodextrin (2HPßCD) as the hydrogen bond donor (HBD), deep eutectic solvents (DESs) with various water content were prepared at the 4:1 mass ratio of L-arginine to 2HPßCD with 40 to 60% of water, and were studied for its application in transdermal drug delivery system (TDDS). The hydrogen bond networks and internal chemistry structures of the DESs were measured by attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1H-nuclear magnetic resonance spectroscopy (1H-NMR), which demonstrated the successful synthesis of DESs. The viscosity of DES was decreased from 10,324.9 to 3219.6 mPa s, while glass transition temperature (Tg) of the DESs was increased from - 60.8 to - 51.4 °C, as the added water was increased from 45 to 60%. The solubility of ibuprofen, norfloxacin, and nateglinide in DES with 45% of water were increased by 79.3, 44.1, and 3.2 times higher than that in water, respectively. The vitro study of transdermal absorption of lidocaine in DESs showed that the cumulative amounts of lidocaine reached 252.4 µg/cm2, 226.1 µg/cm2, and 286.1 µg/cm2 at 8 h for DESs with 45%, 50%, and 60% of water, respectively. The permeation mechanism of DES with lower content of water (45%) was mainly by changing the fluidization of lipids, while changing the secondary structure of keratin in stratum corneum (SC) at higher water content (50% and 60%). These nonirritant and viscous fluid like DESs with good drug solubility and permeation enhancing effects have broad application prospect in the field of drug solubilization and transdermal drug delivery system.

Green preparation of ß-chitins from squid pens by using alkaline deep eutectic solvents.

Based on the assumption that protein could be removed by the combined mechanism of alkaline induced degradation and strong hydrogen bond interactions of deep eutectic solvents (DESs), ß-chitins were successfully prepared from squid pens by using alkaline DESs formed by potassium carbonate and glycerol. The chemical structures of the DESs were investigated by 1H nuclear magnetic resonance (1H NMR), attenuated total reflection Fourier transform infrared (ATR-FTIR) and molecular modeling, and the physicochemical property of the prepared ß-chitins were characterized. The preparation yields was about 32 %, and DESs with K2CO3/glycerol of 1/10 could be reused for three times while maintaining high preparation yields (31 %-32 %) and degree of deacetylation of 66.9 %-76.9 %. The mechanisms of deproteinization and demineralization by the alkaline DESs were proposed to follow the degradation and dissolution steps, and proteins and minerals were removed from squid pens through the synergistic actions of alkaline degradation and hydrogen bonding interactions. This alkaline DESs are promising to be used as a green and efficient approach for commercial production of ß-chitin.

The Study of Deep Eutectic Solvent Based on Choline Chloride and L-(+)-Tartaric Acid Diethyl Ester for Transdermal Delivery System.

Deep eutectic solvents (DESs) based on choline chloride (C) and L-(+)-tartaric acid diethyl ester (L) were prepared and used in transdermal drug delivery system (TDDS). The internal chemistry structure including the formation and changes of hydrogen bonds of choline chloride and L-(+)-tartaric acid diethyl ester DES was characterized via attenuated total reflection Fourier transform infrared (ATR-FTIR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The stoichiometric ratio of choline chloride to L-(+)-tartaric acid diethyl ester as well as water content affected the viscosity, glass transition temperature (Tg), and drug solubility of the DES. The viscosity and glass transition temperature of the DES (CL14) prepared at the ratio of 1:4 of choline chloride to L-(+)-tartaric acid diethyl ester were 1.19 Pa·s and - 44.01°C, respectively, and decreased to 0.10 Pa·s and - 55.31°C when 10% water (CL1410) was added. Taking diclofenac diethylamine (DDEA), the nonsteroidal anti-inflammatory drug as model, drug solubility was as high as 60 mg/ml and 250 mg/ml in CL14 and CL1410, respectively. The cumulative amount of DDEA was 4.63 ± 2.67 µg/cm2 and 15.27 ± 4.63 µg/cm2 for CL14 and CL1410, respectively, at 8 h. The mechanism of percutaneous permeability by the DES may be the disturbance of stratum corneum (SC) lipids as well as changes in the protein conformations. CL14 and CL1410 were also verified as low-cytotoxic and nonirritant. Therefore, the DESs studied are promising to be used in drug solubilization enhancement and transdermal drug delivery system.