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1.
Nutr Res ; 40: 48-56, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28473060

ABSTRACT

Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control. The OVX/T1DM and OVX/T1DM+Zn groups had significantly higher serum alkaline phosphatase activity than the control. The supplemented group had higher levels of serum-ionized calcium and phosphorus than the nonsupplemented group. The RANKL/OPG ratio was similar between the control and OVX/T1DM+Zn groups, whereas it was higher in the OVX/T1DM group. In conclusion, Zn supplementation prevents bone alteration in chronic OVX/T1DM rats, as demonstrated by the reduced RANKL/OPG ratio and preservation of bone architecture. The findings may represent a novel therapeutic approach to preventing OVX/T1DM-induced bone alterations.


Subject(s)
Bone Density/drug effects , Diabetes Mellitus, Experimental/drug therapy , Dietary Supplements , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Zinc/administration & dosage , Alkaline Phosphatase/blood , Animals , Blood Glucose/metabolism , Bone and Bones/drug effects , Calcium/blood , Diabetes Mellitus, Type 1/drug therapy , Female , Osteoprotegerin/genetics , Ovariectomy , Phosphorus/blood , RANK Ligand/genetics , Rats , Rats, Wistar
2.
AAPS PharmSciTech ; 18(6): 2026-2036, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27966176

ABSTRACT

The treatment of peptic ulcers induced by H. pylori remains challenging due to the deep mucous layer location of bacteria preventing antimicrobial drug access. The present work aimed to design and evaluate in vitro dual responsive (both pH and magnetic field-sensitive) polymeric magnetic particles loaded with amoxicillin as a smart drug carrier for deep mucous layer penetration and in situ drug release. Magnetite particles were produced by the co-precipitation method and subsequently coated with the Eudragit®S100 and amoxicillin by using the spray-drying technique. The physicochemical characterization of the obtained particles was carried out by optical and scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, nitrogen adsorption/desorption isotherms, and vibrating sample magnetometry. Additionally, drug release tests and antibacterial activity tests were evaluated in vitro. Microparticles presented 17.2 ± 0.4 µm in size and their final composition was 4.3 ± 1.5% of amoxicillin, 87.0 ± 2.3% of Eudragit, and 9.0 ± 0.3% of magnetite. They were both pH and magnetic field responsive while presenting antimicrobial activity. On one side, magnetic field responsiveness of particles is expected to prompt them to reach bacterium niche in deep mucous layer by means of magnetic forces. On the other side, pH responsiveness is expected to enable drug release in the neutral pH of the deep mucous layer, preventing undesired delivery in the acidic gastric lumen. Smart microparticles were designed presenting both pH and magnetic field responsiveness as well as antimicrobial activity. These may be promising assets for peptic ulcer treatment.


Subject(s)
Amoxicillin/chemical synthesis , Anti-Infective Agents/chemical synthesis , Drug Carriers/chemical synthesis , Gastrointestinal Agents/chemical synthesis , Magnetic Phenomena , Amoxicillin/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Drug Carriers/pharmacology , Drug Compounding/methods , Gastrointestinal Agents/pharmacology , Helicobacter pylori/drug effects , Microscopy, Electron, Scanning/methods , Particle Size , Polymers/chemistry , Spectroscopy, Fourier Transform Infrared/methods , X-Ray Diffraction/methods
3.
Nutr Res ; 40(apr): 48-56, 2017.
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1064952

ABSTRACT

Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control...


Subject(s)
Diabetes Mellitus , Rats , Zinc
4.
J Biomed Nanotechnol ; 8(2): 290-300, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22515080

ABSTRACT

Amphotericin B remains the drug of choice for the treatment of most of the systemic fungal infections in immunodeficient patients. Because of the high incidence of adverse drug reactions the clinical use of Amphotericin B is rather limited. To reduce its toxicity new drug delivery systems has been suggested. Nevertheless, these carriers present several technological drawbacks that impair the development of a marketable product. The aim of this work was to develop an Amphotericin B microemulsion in order to increase its efficacy and decrease its toxicity compared to Fungizon, the widely know inexpensive micellar system of Amphotericin B. Amphotericin B loaded microemulsion showed an average size close to 300 nm by photon correlation spectroscopy. In the UV spectrum, the observation of the monomeric peak at 405 nm, which was independent of the sample dilution, revealed that the Amphotericin B molecules were strongly and individually bound to the microemulsion droplets. The new microemulsion formulation had the same efficacy than Fungizon against C. albicans. Concerning toxicity, Amphotericin B loaded microemulsion showed lower toxicity against human red blood cells compared to the commercial product. Taken together, these results suggested that microemulsion is an eligible drug carrier for Amphotericin B or other water insoluble molecules, and it has potential applications to targeting fungal cells. Additionally, a novel formulation of Amphotericin B-loaded microemulsion was prepared by a straightforward and fast procedure.


Subject(s)
Amphotericin B/chemistry , Amphotericin B/toxicity , Antifungal Agents/chemistry , Antifungal Agents/toxicity , Drug Carriers/chemistry , Drug Carriers/toxicity , Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Candida albicans/drug effects , Cell Survival/drug effects , Drug Carriers/pharmacology , Emulsions/chemistry , Emulsions/pharmacology , Emulsions/toxicity , Erythrocytes/drug effects , Erythrocytes/metabolism , Hemoglobins/metabolism , Humans , Linear Models , Male , Nanoparticles/adverse effects , Nanoparticles/chemistry , Nanoparticles/toxicity , Particle Size , Potassium/blood , Spectrophotometry
5.
Exp Parasitol ; 123(4): 309-12, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19698711

ABSTRACT

With the aim of investigating the biodistribution of technetium-99m pertechnetate ((99m)TcO4-) in rats infected with Y strain of Tripanosoma Cruzi, at the peak of parasitemia, (14th day of infection), we injected Wistar rats with 0.1 ml of (99m)TcO4- (3.7MBq). After 60 min, the percentage of radioactivity per gram was counted in several isolated organs and blood, using a gamma counter (1470 Wizard, PerkinElmer Finland). The uptake of (99m)TcO4- increased significantly in blood and decreased in the colon of infected animals (p<0.05). A significant reduction in serum iron and red blood cells and a significant increase in total proteins, leukocytes and lymphocytes in the infected rats were observed, compared with controls (p<0.05). A reduction in muscle layer thickness of the colon and mononuclear inflammation were observed. These results conclusively demonstrate that T. cruzi infection would be associated with changes in the biodistribution of (99m)TcO4- and in colon morphology, with potential clinical implications.


Subject(s)
Chagas Disease/metabolism , Parasitemia/metabolism , Radiopharmaceuticals/pharmacokinetics , Sodium Pertechnetate Tc 99m/pharmacokinetics , Trypanosoma cruzi/physiology , Animals , Chagas Disease/diagnostic imaging , Chagas Disease/parasitology , Male , Parasitemia/diagnostic imaging , Parasitemia/parasitology , Radionuclide Imaging , Random Allocation , Rats , Rats, Wistar , Tissue Distribution
6.
Int J Pharm ; 334(1-2): 42-7, 2007 Apr 04.
Article in English | MEDLINE | ID: mdl-17113734

ABSTRACT

This work evaluates an experimental set-up to coat superparamagnetic particles in order to protect them from gastric dissolution. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. Afterwards, an emulsification/cross-linking reaction was carried out in order to produce magnetic polymeric particles. The sample characterization was performed by X-ray powder diffraction, laser scattering particle size analysis, optical microscopy, thermogravimetric analysis and vibrating sample magnetometry. In vitro dissolution tests at gastric pH were evaluated for both magnetic particles and magnetic polymeric particles. The characterization data have demonstrated the feasibility of the presented method to coat, and protect magnetite particles from gastric dissolution. Such systems may be very promising for oral administration.


Subject(s)
Ferrosoferric Oxide/chemistry , Magnetics , Polymers/chemistry , Xylans/chemistry , Administration, Oral , Delayed-Action Preparations , Drug Delivery Systems , Ferrosoferric Oxide/chemical synthesis , Hydrogen-Ion Concentration , Lasers , Microscopy, Electron, Scanning , Particle Size , Scattering, Radiation , Solubility , Thermogravimetry , X-Ray Diffraction , Zea mays
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