Preparation of Piroxicam nanosuspensions by high pressure homogenization and evaluation of improved bioavailability.

OBJECTIVE: Inflammation is a natural response of the organism, involving events responsible for releasing chemical mediators and requiring treatments of symptoms such as pain, redness, heat, swelling, and loss of tissue function. Piroxicam (PRX) is a non-steroidal anti-inflammatory drug with the effect of nonselective COX inhibitor activity; however, it shows poor bioavailability caused by the poor and slow water solubility. In this study, we developed PRX nanosuspensions with 200-500 nm in diameter to increase the bioavailability of PRX by improving its solubility. METHODS: PRX nanosuspensions were fabricated by High pressure homogenization method with PVA, SDS and Tween 80. The nanosuspensions were characterized by XRD, FTIR, DSC, and in vitro release. In vivo pharmacokinetic properties and anti-inflammatory effects were also investigated in rabbits. RESULTS: PRX nanosuspensions significantly increased the solubility (14.89 ± 0.03 mg/L for pure PRX and 16.75 ± 0.05 mg/L for PRX nanosuspensions) and dissolution rate as compared to the pure PRX (p < 0.05). Orally administered PRX nanosuspension (AUC 0-t is 49.26 ± 4.29 µg/mL × h) significantly improved the bioavailability of PRX (AUC 0-t is 28.40 ± 12.11 µg/mL × h). The anti-inflammatory effect of PRX nanosuspension was also investigated in rabbits and it was observed that PRX nanosuspension treatment significantly improved the inhibition of COX-2 and NFκB expression as compared to the PRX treatment (p < 0.05). CONCLUSIONS: The results in this study indicate that PRX nanosuspension is a promising nanomedicine for enhancing the anti-inflammatory activity of PRX and has a high potential for the treatment of inflammation.

First detection of heat shock protein 60 and 70 in the serum of early pregnant bitches.

Heat shock proteins (HSPs) belong to a group of cellular stress proteins. Heat shock protein 10 immunoregulates and promotes growth during early gestation in humans, while HSP70 is considered to regulate autophagy and apoptosis during pregnancy and parturition. Both HSPs are detectable in the serum and placentas of early pregnant women and considered to contribute to the establishment of pregnancy. Within this pilot study we aimed (1) to assess whether HSPs 10, 60 and 70 are measurable in the serum of healthy early pregnant and non-pregnant bitches, and (2) to explore whether measurable differences between groups indicate pregnancy. Blood was collected from 31 bitches on days 7, 14 and 21 after mating. At 21 days post mating, all bitches were examined for pregnancy by ultrasonography; 23 were pregnant, and the eight non-pregnant bitches served as controls. Pregnant bitches had normal parturitions and gave birth to healthy puppies. The serum concentrations of HSPs 10, 60 and 70 were measured by electrophoresis and western blot. Serum HSP10 was not detectable. Average serum HSP70 concentration was significantly (d7, P = 0.030; d14, P = 0.023; d21, P = 0.030) lower in pregnant animals at all days investigated, while serum HSP60 was significantly lower at day 21 of gestation (P = 0.024) when compared to the controls. HSP 60 and HSP70 concentrations correlated positively (d7, r = +0.386, P = 0.021; d14, r = 0.450, P = 0.008; d21, r = +0.472, P = 0.006). We conclude that in pregnant bitches, serum concentrations of HSP60 and HSP70 are significantly decreased between days 7 and 21 of gestation, in comparison to non-pregnant bitches in early dioestrus, raising the question about intrauterine functions during the peri-implantation period.

The results of designing a new prototype device and algorithm in closed method intraperitoneal hyperthermia model in rats.

BACKGROUND: There is currently no standard medical device and method available for hyperthermic intraperitoneal therapy studies in rats. In this study, we present our designed device and algorithm that operates based on our own protocol for hyperthermic intraperitoneal treatment in rats. The aim was to demonstrate the effectiveness of the designed device, algorithm, and hyperthermia protocol by showing that the device can achieve the desired temperature inside the rat's abdomen, does not cause rat loss due to complications, operates autonomously, and provides warnings to the operator in case of emergencies. METHODS: A closed method for intraperitoneal hyperthermia protocol was established for 6 female 8-week-old (280-310 g) albino Wistar rats. Fluid inlet and outlet tubes and a temperature probe were inserted through a 1 cm vertical incision between the xiphoid and bladder in the rat's abdomen, and the skin was sutured in a circular manner. A protocol for intraperitoneal hyperthermic treat-ment was established using a saline solution at a flow rate of 100 mL/min for 60 min, maintaining a temperature of 41°C±0.5 inside the rat's abdomen. RESULTS: During the study, a temperature of 41°C±0.5 was successfully achieved in the abdomen of all rats at a flow rate of 100 mL/min±5 for 60 min. Due to three rats reaching a rectal temperature above 38.5°C during the hyperthermia protocol, external cooling was applied to the rat's tail base using ice. There were no losses until the postoperative 72nd h, and the study was successfully completed. CONCLUSION: Our designed device and algorithm, which prioritize animal welfare, operate rapidly, safely, and with high accuracy sensitivity, have been successful in hyperthermic intraperitoneal treatment studies in rats. We believe that they can be used as a stan-dard method and approach in hyperthermic intraperitoneal studies in rats.

Bioactivity of abobotulinum toxin is preserved till 2 weeks upon storage at room temperature: Half body comparative study on rabbit model.

BACKGROUND: Breakages of the cold chain of botulinum neurotoxin A (BONT-A) preparations is not a rare event and occurs due to several unexpected and unintentional reasons during daily practice and intervention schedules could not be proposed due to the lack of data. OBJECTIVE: To investigate the heat stability of abobotulinum toxin A (AboBONT-A) in terms of efficacy and duration of action upon storage at room temperature (25°C) for 2, 4, and 8 weeks. METHODS AND MATERIALS: Twenty rabbits were divided into four groups and received an injection of ideally stored AboBONT-A (Group 1) and stored AboBONT-A for 2 (Group 2), 4 (Group 3), and 8 weeks (Group 4) at room temperature into the anterior auricular muscle. All rabbits were followed up and photographed by weekly for 16 weeks. Grade of paralysis was evaluated by using a modified visual scoring system. RESULTS: No significant alteration was found in initial potency of stored AboBONT-A at room temperature for up to 4 weeks. Storage at room temperature for 2 weeks did not affect the duration of action (group 2; P = .69), and faster recovery was observed in group 3 and group 4. CONCLUSION: The bioactivity of AboBONT-A is not altered till 2 weeks upon storage at room temperature.