In vitro and in vivo effects of chitosan-praziquantel and chitosan-albendazole nanoparticles on Echinococcus granulosus Metacestodes.

Cystic echinococcosis (CE), which is caused by the metacestode of Echinococcus granulosus, is one of the most important zoonoses affecting humans. Benzimidazoles (in particular albendazole) and praziquantel (PZQ) are effective against CE, but poor water solubility of these agents often leads to inadequate results. Here, we evaluate the effects of chitosan-albendazole (ChABZ) and chitosan-praziquantel (ChPZQ) nanoparticles as a new formulation on hydatid cysts both in vitro and in vivo. Developed microcysts in culture were treated with different concentrations of ChABZ and ChPZQ nanoparticles (either alone or in combination), and ABZ + PZQ suspension. The viability rate of microcysts was used to evaluate the drug efficacies. In addition, the prophylactic and therapeutic effects of the drugs were studied on infected DBA/2 mice. Transmission electron microscopy was used to observe the ultra-structural changes. The viability rate of microcysts and differences in cyst weights were compared by ANOVA, and the cyst numbers were compared using the Kruskal-Wallis test. The combination of ChABZ + ChPZQ nanoparticles was more effective than the ABZ + PZQ suspension in vitro (p < 0.05). In prophylaxy, a significant reduction was observed both in size and in number of the cysts in ChABZ + ChPZQ nanoparticle groups compared with the control group (p < 0.05). In the therapeutic stage, however, this treatment only reduced the cyst numbers. Degeneration of the microcysts treated with the drugs was evident in the ultra-structural imaging. Overall, the nanoparticulate drugs were more effective than their suspension counterparts, but further studies are recommended to evaluate the full potential of these nanoparticles in the treatment of human CE.

Comparison between intrathecal and intravenous betamethasone for post-operative pain following cesarean section: a randomized clinical trial.

OBJECTIVE: Inadequate postoperative pain relief after cesarean section can increase complications. In this study, we evaluated the effect of intrathecal betamethasone as an adjunct to bupivacaine on postoperative pain in patients undergoing cesarean section. METHODOLOGY: Ninety-nine patients undergoing cesarean section were assigned to one of three groups. Group 1 (Control) patients received intrathecal bupivacaine, Group 2 patients received intrathecal bupivacaine plus preservative free betamethasone and Group 3 patients received betamethasone intravenously with intrathecal bupivacaine. After surgery, diclofenac in suppository form was administered as needed for analgesia. Postoperative diclofenac requirements, time to first analgesic administration and visual analogue scale pain scores were recorded by a blinded observer. RESULTS: Supplemental analgesic dose requirement with diclofenac for the first 24 hours were significantly less in both groups that received betamethasone compared to the control group (P <0.0001). The mean duration of postoperative analgesia was 336.8±86 min in Intrathecal group and 312.4±106 min in Intravenous group compared with 245.4±93 min in control group (P =0.001). Visual analogue scale scores were significantly less at 4 hours (P<0.0001) and 6 hours (P<0.0001) after surgery in groups that received betamethasone in comparison to control group. The pain scores at 6 hours after surgery were higher in the Intravenous group compared with the Intrathecal group (P = 0.001); However visual analogue scale was not different at 12 and 24 hours after surgery between groups (p > 0.05). CONCLUSION: Intrathecal betamethasone reduced pain and decreased the required dose of diclofenac in 24 hours after cesarean section.

Preparation and characterization of gelatin nanoparticles containing pDNA encoding IL-12 and their expression in CT-26 carcinoma cells.

AIM: Gelatin as a biodegradable, nontoxic and biocompatible natural protein is a good candidate for gene delivery. In this study, pDNA-loaded gelatin nanoparticles were prepared and characterized for the expression of the cytokine IL-12 and anti-tumor effects. MATERIALS & METHODS: Gelatin-pUMVC3-hIL-12 nanoparticles were prepared by the ethanol precipitation technique and evaluated for physicochemical characteristics, cytotoxiciy and transfection efficiency. RESULTS: The prepared particles were spherical in shape with sizes varying from 344.27 to 826.23 nm, ζ-potentials between -944 and -165 mV, and greater than 97% encapsulation efficiency. The particles were nontoxic to CT-26 carcinoma cells. The nanoparticles prepared using 0.5% gelatin solution (G14) with a mean particle size of 816.87 nm (polydispersity index = 0.56 ± 0.01) demonstrated maximum transfection efficiency with 2.5-times higher expression compared with the naked plasmid. CONCLUSION: Gelatin-DNA nanoparticles using 0.5% gelatin solution had minimal cytotoxicity and can be used as a suitable candidate for further gene delivery studies and applications.

Preparation of chitosan-plasmid DNA nanoparticles encoding interleukin-12 and their expression in CT-26 colon carcinoma cells.

PURPOSE: Interleukin-12 (Il-12) as a cytokine has been proved to possess antitumor effects via stimulating the immune system. Non-viral gene delivery systems exhibit low toxicity and are easier to prepare compared to their viral counterparts. In this study, we aimed to prepare plasmid DNA loaded chitosan nanoparticles for expression of Il-12 and to evaluate their physicochemical characteristics, cytotoxicity and transfection efficiency in Murine CT-26 colon carcinoma cells. METHODS: Nanoparticles were prepared using a complex coacervation process at different N/P ratios and characterized in terms of size, zeta potential, polydispersity index, morphology, encapsulation efficiency and polyplex formation. The cytotoxicities and transfection efficiencies of the prepared polyplexes were evaluated by MTT assay and ELISA (for hIL-12, p70), respectively. RESULTS: Size and zeta potential varied from 76.73 to 867.03 nm and between 5.68 and 16.77 mV, respectively. Strong attachment of the DNA to chitosan was observed after polyplex preparation. Encapsulation efficiencies were high (72.97-94.87%). The transfection efficiencies of the prepared complexes were obviously higher than those of naked pDNA when N/P ratios were between 16 and 60. Maximum level of phIL-12 expression was obtained at (N/P = 16) with mean particle size of 381.83±82.77 nm (polydispersity index=0.44) indicating the improved transfection of pUMVC3-hIL12 about 2.80 times compared to that of the naked pUMVC3-hIL12. Prepared polyplexes were nontoxic to CT-26 cells. CONCLUSIONS: Chitosan-DNA nanoparticles at N/P = 16 with minimal cytotoxicity, can be used as suitable candidate for Il-12 delivery. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.