[Preparation and release mechanism of gestodene reservoir-type intravaginal rings].

This study taking gestodene (GEST) as a model, investigated the factors affecting reservoir-type intravaginal ring (IVR)'s drug release. This paper reported a gestodene intravaginal ring of reservoir design, comprising a gestodene silicone elastomer core encased in a non-medicated silicone sheath, separately manufactured by reaction injection moulding at 80 degrees C and heating vulcanization at 130 degrees C is reported. The test investigated the factors affecting drug release through a single variable method, taking the drug release rates of 21 days as standards. When changing the thickness of the controlling sheath outside, the ratio of the first day of drug release and mean daily release (MDR), named the relatively burst effect, is closing to 1 with the thickness of controlling sheath increasing, while the 1.25 mm sheath corresponding to 1.04 controlled the burst release effectively; a positive correlation (r = 0.992 2) existed between the average drug release (Q/t) and drug loading (A) within a certain range. The C6-165 controlling sheath with high solubility of GEST is easier to achieve controlled release of the drug; GEST crystalline power is more effective to implement controlled release of drugs among difficent states of the drug. A 1/4 fractional segment core gives a relatively burst effect of 1.76, while the 1/1 and 1/2 are 1.93 and 1.87 separately, at the same drug loading, concluding that use of a fractional segment core would allow development of a suitable GEST reservoir IVR. In summary, GEST reservoir-type IVR could be adjusted by the thickness of controlling sheath, the loading of drug, the material properties of controlling sheath, the dispersion state of drug, the additive composition and structure of intravaginal ring, to control the drug release behavior and achieve the desired drug release rate.

Hyperthermic Intraperitoneal Chemotherapy plus Intravenous Chemotherapy of Paclitaxel with or without Sintilimab in Gastric Cancer: A Comparative Study.

OBJECTIVE: To compare the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) plus intravenous chemotherapy of paclitaxel with or without sintilimab in peritoneal metastasis of gastric cancer. METHODS: A total of 120 patients assessed for eligibility with peritoneal metastasis of gastric cancer treated in the oncology department of our hospital from January 2019 to June 2020 were recruited. They were concurrently randomly assigned in a 1 : 1 ratio to receive HIPEC plus sintilimab-paclitaxel intravenous chemotherapy (study group) or plus paclitaxel intravenous chemotherapy only (control group). RESULTS: The objective remission rate (ORR) of ascites in the study group was significantly higher than that in the control group. Subgroup analysis showed that an age ≤60 years or well-differentiated tumors were associated with better objective remission. After treatment, significantly higher Karnofsky Performance Status (KPS) scores were observed in the study group versus those of the control group. Adverse events reported were comparable between groups. The study group obtained longer 12-month progression-free survival (PFS) and overall survival (OS) than those of the control group. CONCLUSION: On top of HIPEC, intravenous chemotherapy with sintilimab and paclitaxel constitute an effective alternative for patients with peritoneal metastasis of gastric cancer to enhance ascites remission, ameliorate the quality of life, and prolong survival, versus with paclitaxel alone.

MicroRNA-448 targets SATB1 to reverse the cisplatin resistance in lung cancer via mediating Wnt/ß-catenin signalling pathway.

This study aims to examine whether miR-448 reverses the cisplatin (DDP) resistance in lung cancer by modulating SATB1. QRT-PCR and immunohistochemistry were used to examine the miR-448 and SATB1 expressions in DDP-sensitive and -resistant lung cancer patients. A microarray was used to investigate the cytoplasmic/nucleic ratio (C/N ratios) of genes in A549 cells targeted by miR-448, followed by Dual-luciferase reporter gene assay. A549/DDP cells were transfected with miR-448 mimics/inhibitors with or without SATB1 siRNA followed by MTT assay, Edu staining, flow cytometry, qRT-PCR and western blotting. MiR-448 was lower but SATB1 was increased in DDP-resistant patients and A549/DDP cells. And the patients showed low miR-448 expression or SATB1 positive expression had poor prognosis. SATB1, as a target gene with higher C/N ratios (>1), was found negatively regulated by miR-448. Besides, miR-448 inhibitors increased resistance index of A549/DDP cells, promoted cell proliferation, increased cell distribution in S phrase, declined cell apoptosis and activated Wnt/ß-catenin pathway. However, SATB1 siRNA could reverse the above effect caused by miR-448 inhibitors. MiR-448 targeting SATB1 to counteract the DDP resistance of lung cancer cells via Wnt/ß-catenin pathway.

[Study of the interactions between diorganotin (IV) complexes of 1,3-dimethyl-4-acetyl-5-pyrazolone and mononucleotides and DNA].

AIM: The interactions between diorganotin (IV) complexes of 1,3-dimethyl-4-acetyl-5-pyrazolone (HL1) and mono-nucleotides together with DNA near physiological condition were investigated. METHODS: The mode of action of the diorganotin (IV) complexes with mononucleotides and DNA under different conditions and different times were investigated by high resolution NMR technology and UV spectra. RESULTS: The interaction of [(L1)2SnEt2] with AMP was shown to result in significant change of chemical shift of H(8), H(2) and 31P of AMP. Hyperchromic effect of DNA could be observed due to the interaction of; [(L1)2SnEt2] with DNA, while interaction of [(L1)2SnMe2] with AMP and DNA could only cause obvious change of chemical shift of 31P and lead to hypochromic effect of DNA. CONCLUSION: The results indicate that [(L1)2SnEt2] can selectively bind to the N1 atom of the base and the phosphate oxygen atom of AMP and may further destroy the helical structure of DNA, while the dimethyltin (IV) compound of 1,3-dimethyl-4-acetyl-5-pyrazolone [(L1)2SnMe2] merely binds to the the phosphate oxygen atom of AMP and causes the contraction of DNA helical structure.

Preparation and evaluation of intravaginal ring containing drospirenone.

In the present study, we investigated the feasibility of the vaginal administration of drospirenone silicone IVR. The in vitro release characteristics of matrix-type and reservoir-type IVR were compared under sink conditions in 21 days. At the same time, API excipients compatibility and preformulation study was performed by HPLC, IR, and DSC methods. Biocompatibility of reservoir system was evaluated by tolerability on tissue level in rats. It was found that, under strong light exposure, high temperature, and high humidity conditions, drospirenone and excipients had no significant interactions. The daily release of reservoir-type IVR was about 0.5 mg/d sustaining 21 days, which significantly decreased the burst effect compared with the matrix system. When drospirenone was modified by the PVPk30 in the reservoir system formulation, the daily release rate increased to 1.0 mg/d sustaining 21 days. The cumulative release of reservoir-type IVR was fitted to zero release equation. In addition, biocompatibility of drospirenone IVR system in this dosage is safe. It is feasibility feasibile to further developed for safe, convenient, and effective contraceptive drug delivery with reduced dosing interval.

Preparation and evaluation of proliposomes containing clotrimazole.

Clotrimazole (CT)-containing proliposomes were prepared by penetrating an ethanol solution of CT and Egg phosphatidylcholine (PC) into microporous sorbitol particles, followed by vacuum evaporation of the solvent. As a result, CT proliposomes with free-flowing flowability were obtained. On contact with water, the proliposomes were rapidly converted into a liposomal dispersion, in which a certain amount of CT was entrapped by the liposomes. The result in scanning electronic micrograph confirmed the formation of liposomes structures from proliposomes, and the particles revealed round or ellipse. The ratio of drug to total lipid, ratio of PC to cholesterol and ratio of lipid to sorbitol affected the entrapment efficiency (EE%). The EE% of optimized formulation (CT 10 mg, 0.1 g total lipid, PC/CH ratio is 60 : 40 and 1 g sorbitol) in this investigation was 96.2+/-1.5%. The proliposomes system can provide sustaining release in simulated vaginal fluid at 37+/-1 degrees C for 24 h. In-vivo performance of blank proliposomes, a physical mixture of sorbitol and drug, clotrimazole proliposomes and commercial ointment formulation were evaluated using antifungal activity test. At 7 d post-dose, the c.f.u. of C. albicans decreased in proliposomes-treated groups than ointment and the physical mixture (t-Student, p<0.05). The results indicated that CT-containing vaginal proliposomes prolonged drug release and may increase amount of drug retention into the mucosa to result in more antifungal efficacy. In addition, CT-proliposomes did not affect the morphology of vaginal tissues. Therefore, the dosage form might be further developed for safe, convenient, and effective treatment of vaginal candidasis with reduced dosing interval.