ABSTRACT
Objective: To evaluate the acute toxicity of carboxymethyl chitosan-2, 2’ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) and as well as possible effect on microbial growth and in vitro cell cyto-toxicity. Methods: CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2’ ethylenedioxy bis-ethylamine. In vivo acute toxicity, in vitro cyto-toxicity and antimicrobial activity of CMC-EDBE-FA nanoparticle were determined. Results: Vancomycin exhibited the antibacterial activity against vancomycin sensitive Staphylococcus aureus, but CMC-EDBE-FA nanoparticle did not give any antibacterial activity as evidenced by minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), disc agar diffusion (DAD) and killing kinetic assay. Further, the CMC-EDBE-FA nanoparticle showed no signs of in vivo acute toxicity up to a dose level of 1000 mg/kg p.o., and as well as in vitro cyto-toxicity up to 250 μg/mL. Conclusions: These findings suggest that CMC-EDBE-FA nanoparticle is expected to be safe for biomedical applications.
ABSTRACT
Objective:To test the survival ofStaphylococcus aureus (S. aureus) inside lymphocyte that contributes to the pathogenesis of infection and possible anti-inflammatory and antioxidative effect of nanoconjugated vancomycin againstin vivo S. aureus infection in a dose and duration dependent manner.Methods:5×106CFU/mL vancomycin-sensitive S. aureus(VSSA) and vancomycin-resistiveS. aureus (VRSA) were challenged in Swiss male mice for3 days,5 days, 10 days and15days, respectively. Bacteremia and inflammatory parameters were observed to evaluate the duration for development ofVSSA andVRSA infection.100mg/kg bw/day and500 mg/kg bw/day nanoconjugated vancomycin were administrated toVSSA andVRSA infected group for5days. Bacteremia, inflammatory parameters and oxidative stress related parameters were tested to observe the effective dose of nanoconjugated vancomycin againstVSSAandVRSA infection. Nanoconjugated vancomycin was treated at a dose of100 mg/kg bw/day and500 mg/kg bw/day, respectively, toVSSA andVRSA infected group for successive5 days,10 days and 15 days. Bacteremia, inflammatory parameters and oxidative stress related parameters were observed to assess the effective duration of nanoconjugated vancomycin againstVSSAand VRSA infection.Results: The result revealed thatin vivoVSSA andVRSA infection developed after 5 days of challenge by elevating theNO generation in lymphocyte and serum inflammatory markers. Administration with nanoconjugated vancomycin toVSSA andVRSA infected group at a dose of100 mg/kg bw/day and500 mg/kg bw/day, respectively, for successive10 days eliminated bacterimia, decreasedNO generation in lymphocyte, serum inflammatory markers and increased antioxidant enzyme status.Conclusions:These findings suggest,in vivochallenge ofVSSA andVRSA for5 days can produce the highest degree of damage in lymphocyte which can be ameliorated by treatment with nanoconjugated vancomycin for10 successive days.
ABSTRACT
Objective: To evaluate the potency of carboxymethyl chitosan-2, 2’ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) on tissue injury, antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice. Methods:CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2’ ethylenedioxy bis-ethylamine. Animals were divided into four groups, i.e., control, nicotine (1 mg/kg bw/day), CMC-EDBE-FA (1 mg/kg bw/day) and nicotine (1 mg/kg bw/day) and CMC-EDBE-FA (1 mg/kg bw/day) for 7 days. Levels of lipid peroxidation, oxidized glutathione level, antioxidant enzyme status and DNA damage were observed and compared. Results: The significantly increase of lipid peroxidation, oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group; those were significantly reduced in CMC-EDBE-FA supplemented group. Moreover, significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA. Only CMC-EDBE-FA treated groups showed no significant change as compared with control group; rather than it repairs the tissue damage of nicotine treated group. Conclusions: These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity.