Nanoconjugated vancomycin: new opportunities for the development of anti-VRSA agents.

More than 90% of Staphylococcus strains are resistant to penicillin. In 1961 S. aureus developed resistance to methicillin (MRSA), invalidating almost all antibiotics, including the most potent beta-lactams. Vancomycin, a glycopeptide antibiotic, was used for the treatment of MRSA in 1980. Vancomycin inhibits the bio-synthesis of peptidoglycan and the assembly of NAM-NAG-polypeptide into the growing peptidoglycan chain. Vancomycin resistant S. aureus (VRSA) first appeared in the USA in 2002. Folic acid tagged chitosan nanoparticles are used as Trojan horses to deliver vancomycin into bacterial cells. These nanoparticles are biocompatible and biodegradable semisynthetic polymers. These nanosized vehicles enhance the transport of vancomycin across epithelial surfaces and show its efficient drug action, which has been understood from studies of the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles of a chitosan derivative loaded with vancomycin. Tolerance values distinctly show that vancomycin loaded into nanoconjugate is very effective and has a strong bactericidal effect on VRSA.

In vitro evaluation of folic acid modified carboxymethyl chitosan nanoparticles loaded with doxorubicin for targeted delivery.

The development of smart targeted nanoparticle that can deliver drugs to direct cancer cells, introduces better efficacy and lower toxicity for treatment. We report the development and characterizations of pH-sensitive carboxymethyl chitosan modified folic acid nanoparticles and manifest their feasibility as an effective targeted drug delivery vehicle. The nanoparticles have been synthesized from carboxymethyl chitosan with covalently bonded bifunctional 2,2'-(ethylenedioxy)-bis-(ethylamine) (EDBE) through the conjugation with folic acid. The conjugation has been analyzed by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The resultant nanoparticles with an average size less then 200 nm measured by dynamic light scattering and transmission electron microscopy. Confocal microscopy and flow cytometric analysis have revealed that folate-mediated targeting significantly enhances the cellular uptake of the nanoparticle and thus facilitates apoptosis of cancer cells (HeLa, B16F1). For the application of the nanoparticles as a drug carrier, Doxorubicin a potent anticancer drug has been loaded into the nanoparticles, with the drug loading amount and the drug release pattern observed.

Potent suppression of agglutinability of human A and B type erythrocytes by KMnO(4)-EDTA concerted action.

PURPOSE OF THE STUDY: Study was focused to effectively suppress the agglutinability of human A and B type erythrocyte by concerted chemical oxidation approach. Consequently some major bio-physiological consequences of human erythrocytes were analyzed. MATERIALS AND METHODS: Concerted chemical oxidation of human A and B type erythrocyte were done by potassium permanganate (KMnO(4)) in presence of ethylene diamine tetra-acetic acid (EDTA). All the chemical reactions were carried out at 37°C temperature and pH 7.4 in phosphate buffer. Finally, suppression of agglutinability were determined by using anti-A and anti-B antisera. RESULTS: A marked suppression in agglutinability was observed after chemical treatment on human A and B type erythrocytes in vitro. Effective suppression of agglutinability was observed in 0.57 mM concentration of KMnO(4) in presence of 0.9 mM EDTA at optimum condition. CONCLUSIONS: Results showed that KMnO(4)-EDTA concerted action is feasible. The future work is directed towards the universal human erythrocytes preparation from A and B type human erythrocytes.