Design, formulation and evaluation of sustained release bilayer tablets of ciprofloxacin hydrochloride

The present research work involve the development of a bilayer tablet of ciprofloxacin hydrochloride using a superdisintegranting agent (sodium starch glycolate) for the fast releasing layer and hydrophobic polymers like ethyl cellulose, acrycoat L100 and acrycoat S100 for the delayed releasing layer. Ciprofloxacin was used as a model drug. Tablets were prepared by wet granulation method. The prepared bilayer tablets were evaluated for angle of repose, bulk density, tapped density, Carr’s index, Hausner’s ratio at the precompression stage and thickness variation, weight variation, hardness, friability, drug content, disintegration time,  in vitro drug release study at the post compression stage.. In vitro dissolution studies were carried out in a USP 24 apparatus I. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 12 h from optimized formulations was observed. Present research work involves the development of a bilayer tablet of ciprofloxacin hydrochloride using a superdisintegrant for the fast releasing layer and hydrophobic polymers for the delayed releasing layer. There was the initial burst effect from the formulations to provide the loading dose of the drug, followed by sustained release to provide maintenance dose of the drug. Keywords: Superdisintegrants, Burst release, Wet granulation, non-Fickian, Sustained releas

A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

BACKGROUND: In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone) glycinate (CuNG) has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS) generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing Swiss albino mice. METHODS: The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1) expression and on activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). RESULTS: CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH) within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. CONCLUSION: Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic

Berberine Chloride Mediates Its Anti-Leishmanial Activity via Differential Regulation of the Mitogen Activated Protein Kinase Pathway in Macrophages

BACKGROUND: A complex interplay between Leishmania and macrophages influences parasite survival and necessitates disruption of signaling molecules, eventually resulting in impairment of macrophage function. In this study, we demonstrate the immunomodulatory activity of Berberine chloride in Leishmania infected macrophages. PRINCIPAL FINDINGS: The IC(50) of Berberine chloride, a quaternary isoquinoline alkaloid was tested in an amastigote macrophage model and its safety index measured by a cell viability assay. It eliminated intracellular amastigotes, the IC(50) being 2.8 fold lower than its IC(50) in promastigotes (7.10 µM vs. 2.54 µM) and showed a safety index >16. Levels of intracellular and extracellular nitric oxide (NO) as measured by flow cytometry and Griess assay respectively showed that Berberine chloride in Leishmania infected macrophages increased production of NO. Measurement of the mRNA expression of iNOS, IL-12 and IL-10 by RT-PCR along with levels of IL-12p40 and IL-10 by ELISA showed that in infected macrophages, Berberine chloride enhanced expression of iNOS and IL-12p40, concomitant with a downregulation of IL-10. The phosphorylation status of extracellular signal related kinase (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK) was studied by western blotting. In infected macrophages, Berberine chloride caused a time dependent activation of p38 MAPK along with deactivation of ERK1/2; addition of a p38 MAPK inhibitor SB203580 inhibited the increased generation of NO and IL-12p40 by Berberine chloride as also prevented its decrease of IL-10. CONCLUSIONS: Berberine chloride modulated macrophage effector responses via the mitogen activated protein kinase (MAPK) pathway, highlighting the importance of MAPKs as an antiparasite target

Deflection control for piezoelectric actuator through voltage signal and it’s application in micromanipulation

Piezoelectric actuator can be used for handling and grasping of miniature parts in micromanipulation where study of stable displacement and force characteristics with voltage are important for developing a micro gripper. In order to obtain these behaviors of piezoelectric actuator, electromechanical characterization of piezoelectric actuator has been carried out in this paper where a mathematical model for deflection and force response of piezoelectric actuator with voltage is derived with the help of a simple first-order model under a step input voltage. This is controlled through a proportional-derivative (PD) controller. Experimentally, it is verified that the piezoelectric actuator attains the maximum deflection upto 1.5 mm and produces force upto 0.203 N by applying voltage (0–60 V). A prototype of novel piezoelectric actuator based micro gripper along with micro manipulation system is developed. By conducting experiments, it is proved that controlled voltage for piezoelectric actuator helps in compensating the misalignment during micro assembly

Analysis of multiple robotic assemblies by cooperation of multimobile micromanipulation systems (M4S)

This paper presents different analyses by cooperation of multimobile micromanipulation systems (M4S) for robotic microassembly where assembly is performed in a grid pattern by dividing it into different zones. To cater this need, a new design of M4S for robotic assembly is proposed where different peg-in-hole assemblies are carried out. For attempting the different combinations by cooperation of M4S, a novel algorithm is developed which provides a solution for robotic microassembly in a more efficient and precise manner within less time. Experientially, it is proved that this novel design of M4S is capable of performing the different manipulation tasks of miniature parts. Different analyses prove its potentiality of robotic assembly in industrial applications

Design and manufacturing of mobile micro manipulation system with a compliant piezoelectric actuator based micro gripper

This paper presents a new design of mobile micro manipulation system for robotic micro assembly where a compliant piezoelectric actuator based micro gripper is designed for handling the miniature parts and compensation of misalignment during peg-in-hole assembly is done because piezoelectric actuator has capability of producing the displacement in micron range and generates high force instantaneously. This adjusts the misalignment of peg during robotic micro assembly. The throughput/speed of mobile micro manipulation system is found for picking and placing the peg from one hole to next hole position. An analysis of piezoelectric actuator based micro gripper has been carried out where voltage is controlled through a proportional-derivative (PD) controller. By developing a prototype, it is demonstrated that compliant piezoelectric actuator based micro gripper is capable of handling the peg-in-hole assembly task in a mobile micro manipulation system

Immunomodulatory role of arabinosylated lipoarabinomannan on Leishmania donovani infected murine macrophages

366-372Arabinosylated lipoarabinomannan (Ara-LAM), a surface glycolipid antigen isolated from avirulent Mycobacterium smegmatis is involved in modulation of host cell signaling. In this study, we investigated Ara-LAM-mediated modulation of impaired immune responses during visceral leishmaniasis caused by protozoan parasite Leishmania donovani. Ara-LAM treatment at dose of 3 μg/ml in L. donovani infected murine peritoneal macrophages as well as J774A.1 macrophage cell line exhibited a distinct up-regulation of pro-inflammatory cytokines like TNF-⍺ and IL-12 both at the protein and transcriptional level. In addition, generation of nitric oxide and iNOS expression were also observed. The present study showed that Ara-LAM was significantly effective in elimination of L. donovani parasites from both peritoneal as well as J774A.1 macrophages. Thus, it could be utilized as an immunomodulatory agent in prevention of leishmanial pathogenesis

CXCL10 Is Critical for the Generation of Protective CD8 T Cell Response Induced by Antigen Pulsed CpG-ODN Activated Dendritic Cells

<div><p>The visceral form of leishmaniasis is the most severe form of the disease and of particular concern due to the emerging problem of HIV/visceral leishmaniasis (VL) co-infection in the tropics. Till date miltefosine, amphotericin B and pentavalent antimony compounds remain the main treatment regimens for leishmaniasis. However, because of severe side effects, there is an urgent need for alternative improved therapies to combat this dreaded disease. In the present study, we have used the murine model of leishmaniasis to evaluate the potential role played by soluble leishmanial antigen (SLA) pulsed-CpG-ODN stimulated dendritic cells (SLA-CpG-DCs) in restricting the intracellular leishmanial growth. We found that mice vaccinated with a single dose of SLA-pulsed DC stimulated by CpG-ODN were protected against a subsequent leishmanial challenge and had a dramatic reduction in parasite burden along with the generation of parasite specific cytotoxic T lymphocytes. Moreover, we demonstrate that the induction of protective immunity conferred by SLA-CpG-DCs depends entirely on the CXC chemokine IFN-γ-inducible protein 10 (CXCL10; IP-10). CXCL10 is directly involved in the generation of a parasite specific CD8⁺ T cell-mediated immune response. We observed significant reduction of CD8⁺ T cells in mice depleted of CXCL10 suggesting a direct role of CXCL10 in the generation of CD8⁺ T cells in SLA-CpG-DCs vaccinated mice. CXCL10 also contributed towards the generation of perforin and granzyme B, two important cytolytic mediators of CD8⁺ T cells, following SLA-CpG-DCs vaccination. Together, these findings strongly demonstrate that CXCL10 is critical for rendering a protective cellular immunity during SLA-CpG-DC vaccination that confers protection against <em>Leishmania donovani</em> infection.</p> </div