Statins in risk-reduction and treatment of cancer.

Statins, which are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications. In addition to this main activity, statins show pleiotropic effects such as antioxidant, anti-inflammatory and antiproliferative properties, with applications in many pathologies. Based on their antiproliferative properties, in vitro and in vivo studies have investigated their effects on various types of cancer (i.e., breast cancer, prostate cancer, colorectal cancer, ovarian cancer, lung cancer) with different genetic and molecular characteristics. Many positive results were obtained, but they were highly dependent on the physiochemical properties of the statins, their dose and treatment period. Combined therapies of statins and cytotoxic drugs have also been tested, and synergistic or additive effects were observed. Moreover, observational studies performed on patients who used statins for different pathologies, revealed that statins reduced the risk of developing various cancers, and improved the outcomes for cancer patients. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.

Liposomal Curcumin Enhances the Effect of Naproxen in a Rat Model of Migraine.

BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.

Liposomal Curcumin is Better than Curcumin to Alleviate Complications in Experimental Diabetic Mellitus.

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.

Investigation into the role of Cu/Zn-SOD delivery system on its antioxidant and antiinflammatory activity in rat model of peritonitis.

BACKGROUND: The current study evaluated the role of delivery system (solution, conventional liposomes and PEG-ylated liposomes) on superoxide dismutase (SOD) antioxidant and antiinflammatory properties in a rat model of lipopolysaccharide (LPS)-induced peritonitis. METHODS: Fifty male albino rats (Wistar-Bratislava) were divided into five groups (n=10). Control group received saline and the other four groups received intraperitoneal injections of LPS (5mg/kg). Among the LPS-injected groups, one was LPS control group and the other three groups received the endotoxin injection 30min after receiving the same dose of SOD (500U/kg, ip) in different delivery systems: saline solution (SOD-S), conventional liposomes (SOD-L) or PEG-ylated liposomes (SOD-PL). The animals were euthanized 6h after LPS injection, blood samples were collected and acute phase response (total and differential leukocytes count; tumor necrosis factor α), antioxidants (total antioxidants; reduced glutathione), oxidative stress (total oxidants; lipid peroxidation) and nitrosative stress (nitric oxide metabolites; nitrotyrosine) were evaluated. RESULTS: Intraperitoneal administration of LPS to rats induced a marked inflammatory and oxidative response in plasma. On the other hand, all SOD formulations had protective effect against endotoxin-induced inflammation and oxidative/nitrosative stress, but PEG-ylated liposomes had the most significant activity. Thus, SOD-PL administration significantly reduced the effects of LPS on bone marrow acute phase response, the oxidative status and production of nitric oxide metabolites, while increasing the markers of antioxidant response in a significant manner. CONCLUSION: SOD supplementation interferes both with inflammatory and oxidative pathways involved in LPS-induced acute inflammation, PEG-ylated liposomal formulation being of choice among the tested delivery systems.

Influence of dextran on the bioadhesive properties of poly(anhydride) nanoparticles.

This work describes the bioadhesive properties of poly(methyl vinyl ether-co-maleic anhydride) (Gantrez AN) nanoparticles (NP) associated with various types of dextran (two hydroxyl-functionalized dextrans and one amino-derivative of dextran). The association of dextran to the polymer was performed either prior NP formation or by the attachment of dextran to the surface of the just formed NP. The amount of dextran associated to the nanoparticles was quantified by a HPLC/ELSD method and dextran presence in the nanoparticles was confirmed by IR spectroscopy, (1)H NMR and in vitro agglutination assay. The in vivo bioadhesion study has demonstrated significantly higher adhesive interactions with the gastrointestinal tract of rats for all types of dextran associated nanoparticles compared with control nanoparticles. For nanoparticles associated with the aminated-dextran, the curves of bioadhesion were characterized by a maximum of adhesion just after administration followed by a rapid and constant decline with time. On the contrary, nanoparticles associated to conventional dextrans displayed a maximum bioadhesion between 1 and 3h post-administration. These results encourage us for further use of these systems for oral delivery of drugs.