ABSTRACT
Fibroin nanoparticles (FNP) have been employed in numerous biomedical applications. However, limited research has focused on the oral delivery of FNP and in-depth molecular interactions between the encapsulated drug and FNP. Therefore, this work developed the FNP, functionalized with poly(vinyl alcohol) (PVA), to orally deliver the zwitterionic ciprofloxacin, focused on the molecular interactions. The particles were formulated using both desolvation (the drug precipitated during the particles formulation) and adsorption (the drug adsorbed on the particles surfaces) methods. The optimal formula possessed a size of ~630 nm with narrow size distribution (measured by DLS method), spherical shape (determined by SEM), and moderate drug loading (confirmed by FT-IR, XRD, and DSC techniques) of ~50% for the desolvation method and ~43% for the adsorption method. More than 80% of the drug molecules resided on the particle surfaces, mainly via electrostatic forces with fibroin. The drug was physically adsorbed onto FNP, which followed Langmuir model and pseudo second-order kinetics. In the in-vitro simulated gastric condition at pH 1.2, the ciprofloxacin bound strongly with FNP via electrostatic forces, thus hindering the drug release (< 40%). Contrastingly, in the simulated intestinal condition at pH 6.8, the particles could control the drug release rates dependent on the PVA amount, with up to ~100% drug release. Lastly, the particles possessed adequate antibacterial activities on Bacillus subtilis, Escherichia coli, and Salmonella enterica, with MIC of 128, 8, and 32 µg/mL, respectively. In summary, the FNP and PVA functionalized FNP could be a potential oral delivery system for zwitterionic drugs.
Subject(s)
Ciprofloxacin , Fibroins , Nanoparticles , Polyvinyl Alcohol , Ciprofloxacin/chemistry , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacology , Polyvinyl Alcohol/chemistry , Fibroins/chemistry , Administration, Oral , Nanoparticles/chemistry , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Particle Size , Drug Carriers/chemistry , Adsorption , Escherichia coli/drug effects , Drug Delivery Systems , Spectroscopy, Fourier Transform Infrared , Microbial Sensitivity TestsABSTRACT
BACKGROUND: Infectious diseases of the central nervous system (CNS) remain common and life-threatening, especially in developing countries. Knowledge of the aetiological agents responsible for these infections is essential to guide empiric therapy and develop a rational public health policy. To date most data has come from patients admitted to tertiary referral hospitals in Asia and there is limited aetiological data at the provincial hospital level where most patients are seen. METHODS: We conducted a prospective Provincial Hospital-based descriptive surveillance study in adults and children at thirteen hospitals in central and southern Viet Nam between August 2007-April 2010. The pathogens of CNS infection were confirmed in CSF and blood samples by using classical microbiology, molecular diagnostics and serology. RESULTS: We recruited 1241 patients with clinically suspected infection of the CNS. An aetiological agent was identified in 640/1241 (52%) of the patients. The most common pathogens were Streptococcus suis serotype 2 in patients older than 14 years of age (147/617, 24%) and Japanese encephalitis virus in patients less than 14 years old (142/624, 23%). Mycobacterium tuberculosis was confirmed in 34/617 (6%) adult patients and 11/624 (2%) paediatric patients. The acute case fatality rate (CFR) during hospital admission was 73/617 (12%) in adults and to 42/624 (7%) in children. CONCLUSIONS: Zoonotic bacterial and viral pathogens are the most common causes of CNS infection in adults and children in Viet Nam.