Hexagonal liquid crystalline system containing cinnamaldehyde for enhancement of skin permeation of sinomenine hydrochloride.

Sinomenine hydrochloride (SH) is usually applied to treat rheumatoid arthritis (RA) with severe side effects due to oral administration. Cinnamaldehyde (CA) as essential oil possesses an anti-RA effect and can facilitate transdermal penetration. Hence, this study developed hexagonal liquid crystalline (HII) gels to deliver two components (SH and CA) across the skins. HII gels were prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and rheology. Moreover, in vitro drug release behavior and ex vivo skin permeation were investigated. Finally, Fourier transforms infrared spectral analysis (FTIR) and confocal laser scanning microscopy (CLSM) were used to explore the skin penetration mechanism. PLM and SAXS showed that the inner structure of the gels was HII phase. The addition of lipophilic or hydrophilic molecules slowed down one another's release and the release model was dominated by Fickian diffusion (n < 0.43). Furthermore, in vitro permeation studies indicated that appropriate CA could improve the skin permeability of SH. FTIR and CLSM suggested that infiltration occurred due to disruption of the lipid bilayer structure and increased fluidity of the skin. In conclusion, HII gels and CA exhibited a penetration-promoting effect for transdermal applications in SH.

In vitro and in vivo evaluation of cinnamaldehyde Microemulsion-Mucus interaction.

The current investigation explores the possible mechanism of the microemulsion drug delivery system to improve the oral bioavailability of cinnamaldehyde (CA), an important food spice, from the perspective of the microemulsion-mucus system. The cinnamaldehyde microemulsion (CA-ME) was prepared by the water titration method combined with the pseudo-ternary phase diagram. The dynamic analysis was applied to detect the drug release in vitro. An intestinal mucosal injury test was conducted to evaluate the safety of CA-ME and drug absorption across the intestinal tract of rats was investigated through an Ussing chamber system. The rheology of blank mucus and drug-loaded mucus was investigated using a rheometer. The bioavailability of CA-ME in rats was evaluated through pharmacokinetic characteristics. The ratio of optimal prescription was Tween 80: 1,2-propanediol: vitamin E oil: CA: water = 24.3:4.8:5:7.5:58.4. The droplets were uniform in size and evenly dispersed. Rheological studies showed that the microemulsion-mucus system all exhibit pseudoplastic fluid behavior, and CA-ME increased the viscosity of the mucus to a certain extent. Compared with CA solution, CA-ME promoted the absorption of CA in various intestinal segments, especially the ileum. Pharmacokinetic experiments showed that the relative bioavailability of CA-ME was enhanced 2.5-fold higher than that of CA solution. ME as a carrier for lipophobic substances, may increase the viscosity of the intestine mucus system to obtain longer residue time and better absorption. PRACTICAL APPLICATIONS: In this study, in vitro absorption Ussing model was combined with rheological and pharmacokinetic analysis to systematically analyze the intestinal mucus mechanism of microemulsion to improve the oral bioavailability of cinnamic aldehyde. It laid the foundation for exploring the absorption and transport of drugs in the intestinal mucus barrier.

Effect of Heat-Input on Microstructure and Toughness of CGHAZ in a High-Nb-Content Microalloyed HSLA Steel.

The effect of various heat inputs on the microstructure and impact toughness of the simulated coarse-grained heat-affected zone (CGHAS) of a niobium microalloyed (0.14 wt.%) low-carbon steel was studied. The results showed that higher impact toughness was achieved at a low heat input of 20 kJ/cm, which resulted from the formation of acicular ferrite laths/plates. They sectioned large prior austenite grains into many smaller regions, resulting in smaller crystallographic grains and high-angle grain boundaries. Conversely, when specimens were simulated with larger heat-inputs (100, 200 kJ/cm), the microstructure of the CGHAZ was predominantly composed of granular bainite plus massive MA constituents, thus impairing the impact toughness.

Effect of Niobium Content on the Microstructure and Mechanical Properties of Simulated Coarse-Grained Heat-Affected Zone (CGHAZ) of High-Strength Low-Alloy (HSLA) Steels.

The effect of Nb-content and heat input rate on the mechanical properties and microstructure of simulated coarse-grained heat-affected zone (CGHAZ) of high-strength low-alloy steel (HSLA) was investigated. While using a low heat input (20 kJ/cm), the toughness of simulated CGHAZ was improved by increasing the Nb-content. The maximum toughness was obtained when the Nb-content was 0.110 wt.% and the heat input was 20 kJ/cm. The samples made at this condition had fine martensite/austenite (M/A-constituent), acicular ferrite and refined austenite grains. As the heat input was increased to 200 kJ/cm, the toughness of simulated CGHAZ was significantly decreased irrespective of the Nb-content because of the formation of coarse austenite grains, low angle grain boundaries, and massive M/A-constituents.

SEDDS facilitate cinnamaldehyde crossing the mucus barrier: The perspective of mucus and Caco-2/HT29 co-culture models.

Self-emulsifying drug delivery systems (SEDDS) have potential applications in the delivery of hydrophobic components. Oral drugs are readily captured and cleared by intestinal mucus, a natural barrier that covers the mucosal epithelium and prevents the entry of foreign substances. In this study, we investigated for the first time the ability of SEDDS to deliver the lipophilic aldehyde cinnamaldehyde (CA-SEDDS) in rat mucus, mucin solution, Caco-2 and Caco-2/HT29 co-culture monolayer systems. CA-SEDDS was characterized by particle size, Zeta potential and the logDSEDDS/release medium. The capacity of CA-SEDDS to enhance mucus permeability was investigated in rat intestinal mucus gel and mucin solution with the period of in 12 h by Transwell® diffusion. We evaluated the potential of CA-SEDDS delivery of CA in a co-culture system of absorptive Caco-2 and mucus-secreting HT29 cells. CA-SEDDS exhibited excellent mucus permeability in mucus and mucin solutions, 5.1- and 2.8-fold higher than the free CA group, respectively. CA-SEDDS penetration increased by 2.5-fold compared with free CA when using the mucus-secreting co-culture cell model as a barrier. The relative oral bioavailability of CA-SEDDS was 242% compared to CA without formulation. These findings suggest that SEDDS exhibited good release and superior mucus permeability, displaying great potential for the future of hydrophobic oral applications.

In Situ Liquid Crystal Gel as a Promising Strategy for Improving Ocular Administration of Dexamethasone: Preparation, Characterization, and Evaluation.

The purpose of this study was to design an in situ liquid crystal gel (ISLG) as an ophthalmic drug delivery system for dexamethasone (DEX) to enhance its eye retention and ocular bioavailability. The in situ liquid crystal gels (ISLGs) were prepared using a phytantriol/PEG400/water (65:30:5, w/w) ternary system. Polarized light microscope (PLM), small-angle X-ray scattering (SAXS), and rheology analysis confirmed that the internal structure of the preparations was Pn3m cubic phase liquid crystal gels with pseudoplastic fluid properties. Meanwhile, in vitro release behavior of the preparations conforms to the Higuchi equation. Corneal penetration experiments showed that compared with DEX sodium phosphate eye drops, DEX-ISLGs(F2) produced a 5.45-fold increase in the Papp value, indicating a significant enhancement of corneal penetration. In addition, in vivo experiments have confirmed that the ISLGs have better biocompatibility and longer retention time in the cornea. Simultaneously, corneal hydration level, eye irritation experiments, and histological observations proved the safety of the preparations. Pharmacokinetic studies have shown that the ISLG could maintain the DEX concentration in aqueous humor for at least 12 h after administration, which significantly improves the bioavailability of the drug. Collectively, these results indicated that ISLG would be a potential drug carrier for the treatment of diabetic retinopathy (DR).

Models to evaluate the barrier properties of mucus during drug diffusion.

Mucus is widely disseminated in the nasal cavity, oral cavity, respiratory tract, eyes, gastrointestinal tract, and reproductive tract to prevent the invasion of pathogenic bacteria and toxins. The mucus layer through its continuous secretion can prevent the passage of macromolecular substances such as pathogenic bacteria and toxins, thereby reducing the occurrence of inflammation. Without a doubt, mucus also hinders oral absorption. The physiological and biochemical properties of intestinal mucus and the different types of mucus barrier models need to be predominated. To find ways to increase the bioavailability of drugs in the future, this article summarizes mucus composition, barrier properties, mucus models, and mucoadhesive/mucopenetrating particles to highlight the information they can afford. Collectively, the review seeks to provide a state-of-the-art roadmap for researchers who must contend with this critical barrier to drug delivery.