Preparation and sustained-release mechanism of hydroxybutyl chitosan/graphene oxide temperature-sensitive hypoglycaemic subcutaneous implants.

The current situation of diabetes prevention and control is extremely severe. For instance, glimepiride (GLM), a third-generation sulfonylurea, demonstrates suboptimal clinical efficacy in oral dosage forms, which underscores the pressing need for the development of a new dosage form. Recently, in situ gel subcutaneous implants have garnered considerable attention. Hydroxybutyl chitosan (HBC) can spontaneously crosslink to form a thermosensitive hydrogel and has good biocompatibility. However, its application is hindered by its limited mechanical properties. Graphene oxide (GO), known for its stable dispersion in water, can load GLM through π-π stacking interactions. When combined with HBC, GO enhances the mechanical properties and stability of the hydrogel. Therefore, an HBC-GO@GLM hydrogel was prepared. Rheological analysis revealed that the incorporation of GO increased the critical gelation temperature of the 5 wt% HBC hydrogel from 19.1°C to 27.2°C, considerably enhancing the mechanical properties of the hydrogel. Using encapsulation efficiency as an evaluation index, the optimal encapsulation efficiency of GO@GLM was determined to be 73.53% ± 0.45% with a drug loading capacity of 27.39 ± 0.17% using the Box-Behnken design model. Computer simulation technology validated the interaction between the materials and the drug release mechanism. Pharmacokinetic results showed that compared to the HBC@GLM group, the half-life (t1/2), mean residence time and the area under the curve for the HBC-GO@GLM group were approximately 3 times those of the HBC@GLM group. Subcutaneous implantation of the HBC-GO@GLM hydrogel for drug delivery considerably extended the drug's action time in the body, thereby maintaining blood sugar levels within a normal and stable range for an extended period.

Preparation and antitumor study of intelligent injectable hydrogel: Carboxymethyl chitosan-aldehyde gum Arabic composite graphene oxide hydrogel.

In this study, we used polyaldehyde gum Arabic (OGA) and carboxymethyl chitosan (CMCS) as a gel matrix to form an injectable self-healing hydrogel by Schiff-base bonding. Further, graphene oxide (GO) was loaded with doxorubicin (DOX) to the hydrogel, which resulted in a CMCS-OGA/GO@DOX hydrogel. We achieved a DOX drug loading capacity of 43.80 ± 1.13 %. Rheological studies showed that GO hydrogels have improved mechanical properties. The in vitro release profile showed pH responsiveness with 88.21 % DOX release at pH 5.5. Biocompatibility studies showed that the hydrogel composition had good cytocompatibility with L929 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed a cell survival rate of 93.88 % within 48 h. The DOX-loaded hydrogel exhibited higher cell mortality in breast cancer cells (4 T1), with an inhibition rate of 79.4 % at 48 h. Acridine orange/ethidium bromide staining experiments on 4 T1 cells showed that when loaded with the same DOX concentration, the hydrogel significantly reduced the toxic effects on normal cells, whereas it had significant cytotoxic effects on cancer cells. This result indicates that the prepared GO hydrogel drug delivery system can serve as a novel approach for localized breast cancer treatment.

Synthesis and evaluation of curcumin-based near-infrared fluorescent probes for detection of amyloid ß peptide in Alzheimer mouse models.

The abnormal accumulation of amyloid ß protein (Aß) is one of the most important causes of Alzheimer's disease (AD) and is usually a detecting biomarker. Curcumin and its derivatives have potential Aß aggregate targeting ability; we synthesized a series of curcumin-based near-infrared fluorescence probes in this study. By characterizing the excitation wavelength and emission wavelength, the imaging characteristics of the investigation in the near-infrared light region were determined; with an increase in the concentration of the probe compounds, the fluorescence intensity showed an upward trend, demonstrating ideal optical characteristics. In vivo, imaging results showed that the synthesized probe compounds could penetrate the blood-brain barrier (BBB) and specifically bind to Aß in the brain of APP/PS1 mice. Especially for compound 3b, the maximum emission wavelength was around 667 nm, and the fluorescence signal intensity in the brain of the APP/PS1 mice model was more than twice that of the wild control group at 120 min after administration, which could display Aß pathological changes. The fluorescent probes designed in this study can become an effective tool for early AD diagnosis and visual detection.

Non-closure of the Free Peritoneal Flap During Laparoscopic Hernia Repair of Lower Abdominal Marginal Hernia: A Retrospective Analysis.

Background: During lower abdominal marginal hernia repair, the peritoneal flap is routinely freed to facilitate mesh placement and closed to conclude the procedure. This procedure is generally called trans-abdominal partial extra-peritoneal (TAPE). However, the necessity of closing the free peritoneal flap is still controversial. This study aimed to investigate the safety and feasibility of leaving the free peritoneal flap in-situ. Methods: A retrospective review was conducted on 68 patients (16 male, 52 female) who underwent laparoscopic hernia repair between June 2014 and March 2021. Patients were diagnosed as the lower abdominal hernia and all required freeing the peritoneal flap during the operation. Patients were divided into 2 groups: one group was TAPE group with the closed free peritoneal flap, another group left the free peritoneal flap unclosed. Analyses were performed to compare both intraoperative parameters and postoperative complications. Results: There were no significant differences in demographic, comorbidity, hernia characteristics and ASA classification. The intra-operative bleeding volume, visceral injury, hospital stay, urinary retention, visual analog scale (VAS) score, dysuria, intestinal obstruction, surgical site infection, mesh infection, recurrence rate and hospital stay were similar among the two groups. Mean operative time of the flap closing procedure was higher than for patients with the free peritoneal flap left in-situ (p = 0.002). Comparisons of postoperative complications showed flap closure resulted in a higher incidence of seroma formation (p = 0.005). Conclusion: Providing a barrier-coated mesh is used during laparoscopic lower abdominal marginal hernia repair, it is safe to leave the free peritoneal flap in-situ and this approach may prevent the occurrence of seromas.

Effects of puerarin on the pharmacokinetics of triptolide in rats.

Context: Puerarin and triptolide are sometimes used together for the treatment of disease in Chinese clinics; however, the drug-drug interaction between puerarin and triptolide is still unknown. Objective: This study investigates the effects of puerarin on the pharmacokinetics of triptolide in rats and clarifies its main mechanism. Materials and methods: The pharmacokinetic profiles of oral administration of triptolide (1 mg/kg) in Sprague-Dawley rats with (test group, n = 6) or without pretreatment (control group, n = 6) with puerarin (100 mg/kg/day for seven days) were investigated. The effects of puerarin on the transport and metabolic stability of triptolide were also investigated using Caco-2 cell transwell model and rat liver microsomes. Results: The results showed that puerarin could significantly increase the peak plasma concentration (from 187.25 ± 15.36 to 219.67 ± 21.52 ng/mL), and decrease its oral clearance (from 4.92 ± 0.35 to 62.46 ± 3.75 ± 0.19 L/h/kg). The Caco-2 cell transwell experiments indicated that puerarin could decrease the efflux ratio of triptolide from 2.70 to 1.33, and the intrinsic clearance rate of triptolide was decreased by the pretreatment with puerarin (38.8 ± 4.7 vs. 32.9 ± 6.5 µL/min/mg protein). Discussion and conclusions: Puerarin could significantly change the pharmacokinetic profiles of triptolide in rats, and it might exert these effects through increasing the absorption of triptolide by inhibiting the activity of P-gp, or through inhibiting the metabolism of triptolide in rat liver. The results also showed that the dose of triptolide should be decreased when these drugs were co-administered.