Hydrogel-encapsulated medium chain lipid-modified zeolite imidazole framework-90 as a promising platform for oral delivery of proteins.

The administration of protein therapeutics through oral means is seen as a convenient and painless experience for patients, making it a significant consideration in the field of drug delivery. Nevertheless, the challenging conditions within the gastrointestinal tract, along with the obstacles to absorption, impede the efficient transportation of proteins. Here, we successfully implemented post-synthetic modifications to attach medium-chain lipids (C10) onto the surface of zeolitic imidazole framework-90 (ZIF-90), then encapsulated the nanoparticles with sodium alginate, resulting in a potential platform for the oral administration of proteins. By means of biomimetic mineralization, ZIF-90 achieves a simple and efficient encapsulation of proteins of varying sizes, while shielding them against degradation by digestive enzymes. Sodium alginate hydrogel protects proteins against gastric acid and helps the cargo to rapidly penetrate the mucus layer. Through a mixed mechanism dominated by micropinocytosis, the C10-conjugated ZIF-90 (ZIF-90-C10) can be uptake by Caco-2 cells with a 200-400% increase and transported through the Golgi apparatus after escaping from lysosomes, exhibiting enhanced uptake in the overall gastrointestinal tract. Furthermore, ZIF-90-C10 retains its adenosine triphosphate-responsive release, which drastically lowers the likelihood of accumulation in vivo and allows targeted delivery for disease cells. Our work highlights mid-chain lipid conjugation as a potent approach to enhancing nanoparticle delivery efficiency and a potential strategy for oral delivery of biomacromolecules when combined with pH-responsive gels.

Directed Self-Assembly of Heterologously Expressed Hagfish EsTKα and EsTKγ for Functional Hydrogel.

Hagfish slime proteins have long been considered useful due to their potential applications in novel green, environmental, and functional bionic materials. The two main component proteins in the slime thread of hagfish, (opt)EsTKα and (opt)EsTKγ, were used as raw materials. However, the methods available to assemble these two proteins are time- and labor-intensive. The conditions affecting protein self-assembly, such as the pH of the assembly buffer, protein concentration, and the protein addition ratio, were the subject of the present research. Through a series of tests, the self-assembly results of a variety of assembly conditions were explored. Finally, a simplified protein self-assembly method was identified that allows for simple, direct assembly of the two proteins directly. This method does not require protein purification. Under the optimal assembly conditions obtained by exploration, a new gel material was synthesized from the hagfish protein through self-assembly of the (opt)EsTKα and (opt)EsTKγ. This assembly method has the benefits of being a simple, time-saving, and efficient. The self-assembled protein gel products were verified by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and contained (opt)EsTKα and (opt)EsTKγ proteins. Scanning electron microscopy (SEM) was used to investigate the self-assembled protein gel after freeze-drying, and it was observed that the self-assembled protein formed a dense, three-dimensional porous network structure, meaning that it had good water retention. Evaluation of the gel with atomic force microscopy (AFM) indicated that the surface of the protein fiber skeleton show the network-like structure and relatively smooth. Characterization by circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR) demonstrated that the two proteins were successfully assembled, and that the assembled protein had a secondary structure dominated by α-helices. The rheological properties of the self-assembled products were tested to confirm that they were indeed hydrogel property.

Synthesis and pH-stimuli responsive research of gemini amine-oxide surfactants containing amides.

The series of gemini amine-oxide surfactants with the formula C n H2n+1CONH(CH2)2N+O-(CH3)-(CH2)3-(CH3)N+O-(CH2)2NHCOC n H2n+1 (n = 11, 13, 15, and 17) has been synthesized successfully. Their isoelectric point and acid dissociation constant were measured to determine the ionization form of the surfactant molecules in aqueous solution within different pH values. The studies showed that the length of the hydrophobic alkyl chains had a great influence on the pH-stimuli responsive behavior of these surfactants. When n ≤ 13 (n-3-n-OA), the regularity of the pH-stimuli responsive behavior of the surfactant solutions was relatively consistent, while the surfactants with longer hydrophobic alkyl chain lengths lost this regularity (n ≥ 15). In addition, vesicles were observed in most of these surfactant aqueous solutions, with the exception of 11-3-11-OA. Moreover, the obvious flocculation phenomenon was observed within the range of pH 4-5, and they flocculated rapidly when they approached their isoelectric points. This process was reversible, which brought more possibilities for their application in drug delivery and release.

The surface adsorption, aggregate structure and antibacterial activity of Gemini quaternary ammonium surfactants with carboxylic counterions.

A group of Gemini quaternary ammonium surfactants with the formula C n H2n+1CONH(CH2)2N+(CH3)2(CH2)2N+(CH3)2(CH2)2 NHCOC n H2n+1 · 2Y (n = 11, 13 and 15, Y = HCOO-, CH3COO- and CH3CHOHCOO-) have been synthesized by a counterion conversion process and characterized by Fourier transform infrared spectroscopy and mass spectroscopy. Their adsorption and self-aggregation properties are investigated by surface tension, conductivity, dynamic light scattering and transmission electron microscopy (TEM) measurements. The results show that these surfactants reduce the surface tension of water to a minimum value of 26.51 mN m-1 at a concentration of 5.72 × 10-2 mmol l-1. Furthermore, the increased alkyl chain length of the carboxylic counterions leads to the increased critical micelle concentration, the decreased degree of counterion binding (ß) and the decreased self-assembly tendency, but the minimum area per surfactant molecule (A min) adsorbed at the air-aqueous solution are similar. TEM images reveal that these surfactants self-assemble spontaneously into aggregates with vesicle or bilayer structures. It is also found that they have superior antibacterial activity at a concentration of 0.1 g l-1. The high surface activity and high antibacterial activity of the Gemini quaternary ammonium salt surfactants containing different carboxylic counterions bring more possibilities for the application in the field of biomedicine.

[Analysis of main flavonoids contents of Scutellaria baicalensis].

OBJECTIVE: To develop a HPLC-DAD method for simultaneous determination of six flavonoids in Scutellaria baicalensis, and study the effect of geographic sources, culturation, harvesting time and processing on the contents of flavonoids. METHOD: The analysis was performed on a Thermo ODS-2 Hypersil column (4.6 mm x 250 mm, 5 microm) at 26 degrees C with a gradient program of acetonitrile-0.1% H3 PO4 aqueous solution-tetrahydrofuran as the mobile phase and a Diode Array Detector as the detector with the detection wavelength at 274 nm. The flow rate was 1.0 mL x min(-1), and the injection value was 20 microL. RESULT: Six flavonoids, baicalin (1), oroxylin A-7-O-glucuronide (2), wogonoside (3), baicalein (4), wogonin (5) and oroxylin A (6), were linear over the selected range with R2 > or = 0.999 3. The average recoveries were between 96.6% -103.0%, and RSD were less then 5.0% (n = 9) for flavonoids 1-6. By analyzing the data obtained, the effect of geographic sources, culturation, harvesting time and processing on the contents of flavonoids were discussed. CONCLUSION: This method is simple, sensitive, reliable and reproducible. It can be used for the quality control of S. baicalensis.