Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM —60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw—STZ + CC1, 2 mg/100g bw—STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw—STZ + lCC1, 2 mg/100g bw—STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.

BackgroundCurcumin has antioxidative properties that could be useful in various diseases due to its ability to act on multiple targets of various cellular pathways. We aimed to assess the efficacy of liposomal curcumin compared with curcumin solution, when in addition to sumatriptan (ST) treatment, in an experimental migraine model induced with nitroglycerin (NTG) in rats.MethodsSeven groups of 9 rats each were investigated: control group without migraine (1 mL saline solution intraperitoneal injection [ip]), control group with induced migraine, NTG+ST group (ST), NTG+ST+curcumin1 (CC1) group – 1 mg/100 g body weight (bw), NTG+ST+CC2 – 2 mg/100 g bw, NTG+ST+liposomal curcumin1 (lCC1) group – 1 mg/100 g bw, and NTG+ST+lCC2 (lCC2) group – 2 mg/100 g bw. NTG and ST were administered as 1 mL ip NTG | 1 mg/100 g bw and 1 mL ip ST | 1 mg/100 g bw, respectively. Plasma total oxidative stress (TOS), malondialdehyde (MDA), nitric oxide (NOx), thiol levels, as well as total antioxidative capacity (TAC) were assessed. The nociception process was assessed by counting the number of flinches and shakes after the formalin test.ResultsThe plasma TOS, MDA, and NOx levels, as oxidative stress parameters, were significantly decreased in the curcumin-treated groups, especially where curcumin was in liposomal form. The thiol and TAC were also improved by the curcumin treatment, with the best results obtained for the liposomal curcumin. The closest number of flinches and shakes to the control group was obtained for the group treated with liposomal curcumin at a dose of 2 mg/100 g bw.ConclusionLiposomal curcumin in a dose of 2 mg/100 g bw when in addition to ST treatment could be an optimum therapeutic strategy for migraine attacks and could represent a base for future clinical research and application.

Strategies to improve vaccine efficacy are still required, especially in the case of chronic infections, including human immunodeficiency virus (HIV). DNA vaccines have potential advantages over conventional vaccines; however, low immunological efficacy has been demonstrated in many experiments involving large animals and in clinical trials. To improve the immunogenicity of DNA vaccines, we have designed a plasmid vector exploiting the binding capacity of the bovine papillomavirus E2 protein and we have used electroporation (EP) to increase DNA uptake after intradermal inoculation. We demonstrated, in nonhuman primates (NHPs), efficient induction of anti-HIV immunity with an improved DNA vaccine vector encoding an artificial fusion protein, consisting of several proteins and selected epitopes from HIV-1. We show that a DNA vaccine delivery method combining intradermal injection and noninvasive EP dramatically increased expression of the vaccine antigen selectively in the epidermis, and our observations strongly suggest the involvement of Langerhans cells in the strength and quality of the anti-HIV immune response. Although the humoral responses to the vaccine were transient, the cellular responses were exceptionally robust and persisted, at high levels, more than 2 years after the last vaccine boost. The immune responses were characterized by the induction of significant proportions of T cells producing both interferon-gamma and interleukin-2 cytokines, in both subpopulations, CD4(+) and CD8(+). This strategy is an attractive approach for vaccination in humans because of its high efficacy and the possible use of newly developed devices for EP.

Background and ObjectivesPreviously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation.MethodsA single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography–tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (Cmax), the area under the plasma concentration–time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUCt) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90 % confidence intervals.ResultsThe pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the Cmax, AUCt and AUC∞ values fell within the 80–125 % acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78 %) and ibuprofen (96.45 %) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination.ConclusionConcomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of either drug. The IV and oral dose forms of such a combination are pharmacokinetically equivalent.

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