RESUMEN
BACKGROUND AND AIM: Extensively drug-resistant (XDR) Klebsiella pneumoniae represent a major threat in intensive care units. The aim of the current study was to formulate a niosomal form of azithromycin (AZM) and to evaluate its in vitro effect on XDR K. pneumoniae as a single agent or in combination with levofloxacin. MATERIAL AND METHODS: Forty XDR K. pneumoniae isolates (23 colistin-sensitive and 17 colistin-resistant) were included in the study. Formulation and characterization of AZM niosomes were performed. The in vitro effect of AZM solution/niosomes alone and in combination (with levofloxacin) was investigated using the checkerboard assay, confirmed with time-kill assay and post-antibiotic effect (PAE). RESULTS: The AZM niosome mean minimal inhibitory concentration (MIC) (187.4 ± 209.1 µg/mL) was significantly lower than that of the AZM solution (342.5 ± 343.4 µg/mL). AZM niosomes/levofloxacin revealed a 40% synergistic effect compared to 20% with AZM solution/levofloxacin. No antagonistic effect was detected. The mean MIC values of both AZM niosomes and AZM solution were lower in the colistin-resistant group than in the colistin-sensitive group. The mean PAE time of AZM niosomes (2.3 ± 1.09 h) was statistically significantly longer than that of the AZM solution (1.37 ± 0.5 h) (p = 0.023). CONCLUSION: AZM niosomes were proved to be more effective than AZM solution against XDR K. pneumoniae, even colistin-resistant isolates.
Asunto(s)
Antibacterianos/farmacología , Azitromicina/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Levofloxacino/farmacología , Antibacterianos/química , Azitromicina/química , Composición de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Klebsiella pneumoniae/crecimiento & desarrollo , Liposomas/química , Liposomas/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
The study aimed to develop a patient-friendly acyclovir gel with improved efficacy in viral mouth infections, in response to patients' need for an intraoral acyclovir product. Acyclovir was loaded in lipid nanocapsules in gel form, and formulae were evaluated for oromucosal delivery. Lipid nanocapsules were prepared by the phase inversion method. Formulae were optimized to achieve maximum acyclovir entrapment and minimum acyclovir precipitation. Colloidal properties, and pharmaceutical performance indicators were assessed. Drug-loaded lipid nanocapsules were in the nanorange (39-120â¯nm), PdI (0.03-0.2), negative zeta potential, and entrapment efficiency (33-64%). Acyclovir (0.3% w/w) lipid nanocapsules gels were prepared using hydroxyethylcellulose (3% w/w). Resulting gel attributes were considered suitable. Lipid nanocapsules gels (0.3% w/w) showed enhanced Ex vivo acyclovir permeation across, and comparable retention in chicken pouch membrane compared to the 5% marketed cream despite lower drug content. The data provides basis for future exploration of lipid nanocapsules as carrier for transmucosal delivery of acyclovir; the enhanced acyclovir retention in chicken pouch membrane, compared to controls, suggests suitability of lipid nanocapsules for drug delivery to the viral lesion within the buccal membrane.
Asunto(s)
Aciclovir/administración & dosificación , Antivirales/administración & dosificación , Lípidos/administración & dosificación , Mucosa Bucal/metabolismo , Nanocápsulas/administración & dosificación , Aciclovir/química , Administración Oral , Animales , Antivirales/química , Pollos , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Geles , Lípidos/química , Nanocápsulas/químicaRESUMEN
A new vancomycin (VCM)-eluting mixed bilayer niosome formulation was evaluated for the control of staphylococcal colonization and biofilm formation on abiotic surfaces, a niosome application not explored to date. Cosurfactant niosomes were prepared using a Span 60/Tween 40/cholesterol blend (1: 1: 2). Tween 40, a polyethoxylated amphiphile, was included to enhance VCM entrapment and confer niosomal surface properties precluding bacterial adhesion. VCM-eluting niosomes showed good quality attributes including relatively high entrapment efficiency (â¼50%), association of Tween 40 with vesicles in a constant proportion (â¼87%), biphasic release profile suitable for inhibiting early bacterial colonization, and long-term stability at 4°C for a 12-month study period. Niosomes significantly enhanced VCM activity against planktonic bacteria of nine staphylococcal strains. Using microtiter plates as abiotic surface, VCM-eluting niosomes proved superior to VCM in inhibiting biofilm formation, eradicating surface-borne biofilms, inhibiting biofilm growth, and interfering with biofilm induction by VCM subminimal inhibitory concentrations. Data suggest dual functionality of cosurfactant VCM-eluting niosomes as passive colonization inhibiting barrier and active antimicrobial-controlled delivery system, two functions recognized in infection control of abiotic surfaces and medical devices.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Liposomas/química , Staphylococcus aureus/efectos de los fármacos , Vancomicina/administración & dosificación , Vancomicina/farmacología , Biopelículas/crecimiento & desarrollo , Electroquímica , Excipientes , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Polisorbatos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
Marketed topical gels of the antifungal drug naftifine hydrochloride contain 50% alcohol as cosolvent. Repeated exposure to alcohol could be detrimental to skin. The aim of this study is to develop an alcohol-free niosome gel containing 1% naftifine hydrochloride. Niosomes were prepared and formulation variables were optimized to achieve maximum entrapment coupled with stability. Maximum drug entrapment and niosome stability entailed imparting a negative charge to the vesicles where entrapment efficiency reached 50%. Niosomes were incorporated into a hydroxyethylcellulose gel. The final gel contained a total drug concentration of 1% (wt/wt) half of which was entrapped in the niosomes. The results suggest the potential usefulness of the niosome gel.