ABSTRACT
The aim of this work was to prepare polyelectrolyte complexes based on chitosan (CH) and carboxymethylcellulose (CMC) for colon delivery of vancomycin (VM). Various batches of polyelectrolyte complexes, using three different CH/CMC weight ratios (3:1, 1:1 and 1:3), were prepared and collected as microparticles by spray-drying process. Microparticles were characterized in terms of yield, encapsulation efficiency, drug loading, morphology and mucoadhesion properties. Microparticles water-uptake and VM release as well as its protection against gastric pepsin degradation were also investigated. Finally, the antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. The best formulation CH/CMC 1:3 was selected based on the encapsulation efficiency, water-uptake and drug release rate. Moreover, microparticles were able to prevent VM degradation and showed a good antibacterial activity against S. aureus. Finally, to improve the release of VM in the colon the selected formulation was coated with lauric acid.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Colon/metabolism , Drug Carriers/chemistry , Polyelectrolytes/chemistry , Vancomycin/administration & dosage , Animals , Anti-Bacterial Agents/metabolism , Carboxymethylcellulose Sodium/chemistry , Chitosan/chemistry , Hydrogen-Ion Concentration , Lauric Acids/chemistry , Pepsin A/metabolism , Staphylococcus aureus/drug effects , Surface Properties , Swine , Vancomycin/metabolismABSTRACT
The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also measured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle surfaces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Chitosan/chemistry , Drug Delivery Systems , Vancomycin/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Chemistry, Pharmaceutical/methods , Colon/metabolism , Drug Compounding/methods , Drug Liberation , Freeze Drying , Microscopy, Electron, Scanning , Microspheres , Nanoparticles , Particle Size , Polyphosphates/chemistry , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus/drug effects , Technology, Pharmaceutical/methods , Vancomycin/pharmacokineticsABSTRACT
Chitosan/alginate complexes were prepared at different polycation/polyanion molar ratios and freeze-dried vaginal inserts were obtained for chlorhexidine digluconate local delivery in genital infections. Complex yield, FT-IR spectra, and TGA thermograms were studied to confirm the interaction between the two polyions. The influence of different complexes on physical handling, morphology, and drug distribution in the samples were evaluated by friability test, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS), respectively. In vitro water-uptake, mucoadhesion and release tests were performed as well as microbiological tests toward pathogenic vaginal microorganisms. The results showed that the selection of suitable chitosan/alginate molar ratio and drug loading allowed modulate insert ability to hydrate, adhere to the mucosa, and release chlorhexidine digluconate. The insert containing an excess of alginate was found to be the best performing formulation and showed good antimicrobial activity toward the pathogens Candida albicans and Escherichia coli.
