Formulation and Evaluation of a Drug-in-Adhesive Patch for Transdermal Delivery of Colchicine.

Gout is one of the most prevalent rheumatic diseases, globally. Colchicine (COL) is the first-line drug used for the treatment of acute gout. However, the oral administration of COL is restricted, owing to serious adverse reactions. Therefore, this study aimed to develop a drug-in-adhesive (DIA) patch to achieve transdermal delivery of COL. We investigated the solubility of COL in different pressure-sensitive adhesives (PSAs) using slide crystallization studies. The COL-DIA patches were optimized based on in vitro skin penetration studies and evaluated by in vivo pharmacokinetics and pharmacodynamics. The results showed that the optimized COL-DIA patch contained 10% COL, Duro-Tak 87-2516 as PSA, 5% oleic acid (OA) and 5% propylene glycol (PG) as permeation enhancer, exhibiting the highest in vitro cumulative penetration amount of COL (235.14 ± 14.47 µg∙cm-2 over 48 h). Pharmacokinetic studies demonstrated that the maximum plasma drug concentration (Cmax) was 2.65 ± 0.26 ng/L and the mean retention time (MRT) was 37.47 ± 7.64 h of the COL-DIA patch, effectively reducing the drug side effects and prolonging drug activity. In addition, pharmacodynamic studies showed the patch significantly decreased the expression levels of inflammatory factors of gouty rats and reduced pathological damage in the ankle joint of rats, making it an attractive alternative to the administration of COL for the treatment of gout.

Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery.

BACKGROUND: Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). RESULTS: Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. CONCLUSION: DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy.

MicroRNA-490-3p suppresses the proliferation and invasion of hepatocellular carcinoma cells via targeting TMOD3.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It has been reported that microRNAs (miRs) play important roles in the progression and development of HCC. The expression of miR-490-3p has been shown to be downregulated in HCC tissues. Therefore, the present study aimed to investigate the effects of miR-490-3p on HCC cells and the underlying mechanism. Cell Counting Kit-8, flow cytometry, and Transwell migration and invasion assays were performed to determine the viability, apoptosis, migration and invasion of HCC cells, respectively. Furthermore, a luciferase activity assay was used to verify the association between miR-490-3p and its predicted target tropomodulin 3 (TMOD3). In addition, the protein levels of Bax, Bcl-2, cleaved caspase-3, TMOD3, phosphorylated (p)-p38 and p-ERK in HCC cells were detected using western blot analysis. The results demonstrated that the overexpression of miR-490-3p via transfection with miR-490-3p mimics significantly inhibited the proliferation of Huh-7 and HEP 3B2.1-7 cells. In addition, overexpression of miR-490-3p markedly suppressed the migration and invasion abilities of Huh-7 cells. miR-490-3p mimics significantly induced liver cancer cell apoptosis via upregulating Bax and cleaved caspase-3 and downregulating anti-apoptotic protein Bcl-2. Additionally, a luciferase activity assay indicated that TMOD3 is a downstream target gene of miR-490-3p. The protein levels of TMOD3, p-p38 and p-ERK were significantly downregulated in Huh-7 cells following transfection with miR-490-3p mimics, and the overexpression of TMOD3 attenuated these effects. In conclusion, the aforementioned results suggest that the overexpression of miR-490-3p inhibited the proliferation and invasion of HCC cells by targeting TMOD3. Therefore, the miR-490-3p/TMOD3 axis may be a potent target for the treatment of HCC.

Safety and feasibility analysis of combination therapy of laparoscopic left hepatectomy and choledochoscopy for calculus of the left intrahepatic duct.

BACKGROUND: The aim of this paper was to observe the efficacy of combination therapy of laparoscopic left hepatectomy and choledochoscopy for calculus of left intrahepatic duct. METHODS: We retrospectively analyzed the clinical data of 76 patients with calculus of left intrahepatic duct who were admitted and diagnosed in this hospital between August 2014 and August 2015. Patients who received the laparotomy for treatment were enrolled into the control group (N.=32), and those who received the combination therapy of laparoscopic left hepatectomy and choledochoscopy were enrolled into the study group (N.=44). The surgical efficacy and the occurrence of surgery complications were compared between the two groups, and the recurrence of calculus was observed in follow-up after the operation. RESULTS: Comparison of the surgical duration showed no statistically significant difference between the two groups (P>0.05); bleeding amount, evacuation time and length of stay in the study group were less or shorter than those in the control group (P<0.05); the overall incidence rate of surgery complications in the study group was 9.10%, which was lower than the overall incidence rate of surgery complications, 43.75%, in the control group (P<0.05). No statistically significant differences were identified in the comparisons of the levels of albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at 1d before and 10d after operation, hospitalization expenses, and operation fee between the two groups (P>0.05). The average duration of follow-up after operation was 12 months, during which 2 patients in the control group were found with a calculus in a diameter of 0.4 cm in the left intrahepatic duct which was later removed using choledochoscopy followed by the extraction of T duct, and the conditions of patient were well-controlled; no recurrence of calculus was observed in the study group. CONCLUSIONS: Combination therapy of laparoscopic left hepatectomy and choledochoscopy is worth being promoted in clinical practice of treatment for calculus of intrahepatic duct with various advantages, such as significant effect, small trauma, high safety and reliability, rapid recovery after operation and few recurrences.