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Stomach-site specific drug delivery system of clarithromycin for eradication of Helicobacter pylori

Rajinikanth PS, Mishra B

Chem Pharm Bull (Tokyo), 2009 Oct;57(10):1068-75.
PMID: 19801860

Gellan gum based floating beads containing clarithromycin (FBC) were prepared by iontotropic gelation method for stomach-specific drug delivery against Helicobacter pylori. The scanning electron microscope photograph indicated that prepared beads were spherical in shape with rough outer surface. Formulation variables such as concentrations of gellan, calcium carbonate and drug loading influenced the in vitro drug release characteristics of prepared beads. In vitro release rate of clarithromycin was corrected using first order degradation rate constant which is degraded significantly during the release study in simulated gastric fluid pH 2.0. Further, the absence of interactions between drug and polymer was confirmed by differential scanning calorimetry analysis. Kinetic treatment of the in vitro drug release data with different kinetic equations revealed matrix diffusion mechanism. Prepared beads showed good anti-microbial activity against isolated H. pylori strain. The prepared beads have shown good in vivo floating efficiency in rabbit stomach. The stability studies of beads did not show any significant changes after storage of beads at 40 degrees C/75% relative humidity for 6 months. The preliminary results from this study suggest that floating beads of gellan can be used to incorporate antibiotics like clarithromycin and may be effective when administered locally in the stomach against H. pylori.
Fulltext Superior Mesenteric Artery Syndrome in association with Abdominal Tuberculosis: An Eye Opener

Bhatt S, Mishra B, Tandon A, Manchanda S, Parthsarathy G

Malays J Med Sci, 2017 May;24(3):96-100.
PMID: 28814938 DOI: 10.21315/mjms2017.24.3.12

Superior Mesenteric Artery Syndrome (SMAS) is a rare clinical entity presenting as acute or chronic upper gastrointestinal obstruction. It occurs due to compression of third part of duodenum between abdominal aorta and overlying superior mesenteric artery caused by a decrease in angle between the two vessels. Rapid loss of retroperitoneal fat, in conditions leading to severe weight loss is the main factor responsible for this disorder. Superior mesenteric artery syndrome in association with abdominal tuberculosis has not been reported earlier to the best of our knowledge. Therefore, an unknown cause (SMAS) of upper gastrointestinal obstruction in a patient of abdominal tuberculosis is being presented for the first time through this case report. An imaging diagnosis of SMAS was made on contrast enhanced CT abdomen which also confirmed the clinical suspicion of abdominal tuberculosis in the patient. The patient was managed conservatively and recovered without requiring any surgical intervention for the obstructive symptoms.
Lapatinib nano-delivery systems: a promising future for breast cancer treatment

Bonde GV, Yadav SK, Chauhan S, Mittal P, Ajmal G, Thokala S, et al.

Expert Opin Drug Deliv, 2018 05;15(5):495-507.
PMID: 29521126 DOI: 10.1080/17425247.2018.1449832

INTRODUCTION: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.
AREAS COVERED: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.
EXPERT OPINION: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.
Fulltext Isolation, Purification, and Characterization of Heparinase from Streptomyces variabilis MTCC 12266

Singh V, Haque S, Kumari V, El-Enshasy HA, Mishra BN, Somvanshi P, et al.

Sci Rep, 2019 04 24;9(1):6482.
PMID: 31019210 DOI: 10.1038/s41598-019-42740-7

Arterial/venous thrombosis is the major cardiovascular disorder accountable for substantial mortality; and the current demand for antithrombotic agents is extensive. Heparinases depolymerize unfractionated heparin (UFH) for the production of low molecular-weight heparins (LMWHs; used as anticoagulants against thrombosis). A microbial strain of Streptomyces sp. showing antithrombotic activity was isolated from the soil sample collected from north India. The strain was characterized by using 16S rRNA homology technique and identified as Streptomyces variabilis MTCC 12266 capable of producing heparinase enzyme. This is the very first communication reporting Streptomyces genus as the producer of heparinase. It was observed that the production of intracellular heparinase was [63.8 U/mg protein (specific activity)] 1.58 folds higher compared to extracellular heparinase [40.28 U/mg protein]. DEAE-Sephadex A-50 column followed by Sepharose-6B column purification of the crude protein resulted 19.18 folds purified heparinase. SDS-PAGE analysis of heparinase resulted an estimated molecular-weight of 42 kDa. It was also found that intracellular heparinase has the ability to depolymerize heparin to generate LMWHs. Further studies related to the mechanistic action, structural details, and genomics involved in heparinase production from Streptomyces variabilis are warranted for large scale production/purification optimization of heparinase for antithrombotic applications.