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1.
AAPS PharmSciTech ; 19(3): 1454-1467, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29464594

RESUMO

Treatment of bacterial infections becomes increasingly complicated due to increasing bacterial resistance and difficulty in developing new antimicrobial agents. Emphasis should be laid on improvising the existing treatment modalities. We studied the improved antimicrobial and antibiofilm activity of levofloxacin (LFX) and lysozyme (LYS) in microbiological studies. LFX at sub-minimum inhibitory concentration with LYS eradicated > 85% of preformed biofilm. LFX was actively loaded into the liposomes using pH gradient method and was spray-dried with LYS solution. Percent entrapment of LFX in liposome was > 80% and prolonged cumulative release of 85% LFX at the end of 12 h. In vitro lung deposition study and solid-state characterization for spray dried LFX liposome in combination with LYS (LFX liposome-LYS) was performed. Co-spray dried product had mass median aerodynamic diameter ranging < 5 µm. In pharmacodynamic study, Staphylococcus aureus infected rats were treated with LFX liposome-LYS. Lungs, bronchoalveolar lavage fluid (BALF), and nasal fluid were evaluated for microbial burden. Expression of cytokine levels in BALF and serum were also studied by ELISA. In addition, mRNA expression for lung inflammatory mediators and lung myeloperoxidase activity were carried out. Further, lungs and histological changes were observed grossly. Untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels, and microbial load compared to vehicle control. Conversely, LFX liposome-LYS significantly abated these adverse repercussions. Histology findings were also in agreement of above. Acute toxicity study revealed safeness of LFX liposome-LYS. Our findings confirm LFX liposome-LYS exhibited prolonged, improved antibiofilm and antimicrobial efficacy in treating S. aureus infection.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Levofloxacino/uso terapêutico , Pneumopatias/tratamento farmacológico , Muramidase/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Administração por Inalação , Animais , Antibacterianos/administração & dosagem , Quimioterapia Combinada , Levofloxacino/administração & dosagem , Lipossomos , Pneumopatias/metabolismo , Pneumopatias/microbiologia , Pneumopatias/patologia , Muramidase/administração & dosagem , Ratos , Infecções Respiratórias/metabolismo , Infecções Respiratórias/microbiologia , Infecções Respiratórias/patologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus
2.
Nanomedicine ; 13(7): 2371-2384, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28648640

RESUMO

Bacterial resistance remains a major hindrance in treatment with antimicrobial agents. Therefore, we assessed the improved antimicrobial and antibiofilm activity of Levofloxacin (LFX) and Serratiopeptidase (SRP) combinations in in vitro microbiological studies. Further, pharmacodynamic and pharmacokinetic studies of liposomal LFX in combination with SRP (LFX liposome-SRP) were performed in S. aureus infected rats. LFX at sub-MIC with SRP eradicated >90% of the preformed biofilm. The entrapment efficiency of LFX in liposome was >80% and the co-spray dried product had MMAD <5 µm. We observed high LFX concentration in the lung (3.39 µg/ml over 3 h) and AUC/MIC ≥100. In a pharmacodynamic study, untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels and microbial load compared to control. Conversely, LFX liposome-SRP significantly abated these adverse repercussions. Histological findings were also in agreement with these observations. Furthermore, our findings corroborate exhibited improved antibiofilm and antimicrobial efficacy of LFX liposome-SRP in treating S. aureus infection.


Assuntos
Antibacterianos/administração & dosagem , Levofloxacino/administração & dosagem , Pulmão/microbiologia , Peptídeo Hidrolases/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Administração por Inalação , Animais , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Combinação de Medicamentos , Sinergismo Farmacológico , Feminino , Levofloxacino/farmacocinética , Levofloxacino/uso terapêutico , Lipossomos , Pulmão/patologia , Testes de Sensibilidade Microbiana , Peptídeo Hidrolases/farmacocinética , Peptídeo Hidrolases/uso terapêutico , Ratos Wistar , Infecções Estafilocócicas/patologia , Staphylococcus aureus/fisiologia
3.
J Ayurveda Integr Med ; 6(3): 158-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26604550

RESUMO

BACKGROUND: Vetiveria zizanioides (VZ) (family: Poaceae), an aromatic plant commonly known as "Vetiver" has been used for various ailments. Concerning the various ailments being listed as the traditional uses of VZ, no mention about anxiety and memory was found. OBJECTIVE: The present study examined the anxiolytic and memory enhancing activity of ethanolic extract of V. zizanioides (EEVZ) dried roots in mice. MATERIALS AND METHODS: Activity of EEVZ was assessed using models of anxiety (elevated plus-maze [EPM], light/dark test, hole board test, marble-burying test) and learning and memory (EPM, passive shock avoidance paradigm). RESULTS: EEVZ at doses of 100, 200, and 300 mg/kg b.w. illustrated significant anxiolytic activity indicated by increase in time spent and number of entries in open arm, time spent in lightened area, number of head poking and number marble buried when compared to that of diazepam (1 mg/kg b.w.), a reference standard. The same treatment showed a significant decrease in transfer latency to reach open arm, shock-free zone, and number of mistakes when compared to that of scopolamine (0.3 mg/kg b.w.). EEVZ in all the doses (100, 200, and 300 mg/kg b.w.) significantly decreased mortality in sodium nitrite (250 mg/kg b.w.) induced hypoxia and also significantly increases contraction induced by acetylcholine on rat ileum preparation. CONCLUSION: The result emanated in the present investigation revealed EEVZ possesses significant anxiolytic and nootropic activity by possibly interplaying with neurotransmitters implicated in anxiety and learning and memory.

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