Ex-vivo evaluation of alginate microparticles for Polymyxin B oral administration.
A crosslinked alginate microparticle system for the targeting to the lymphatic system by Peyer's patches (PP) uptake was designed in order to improve the oral absorption of Polymyxin B (PMB). To verify mucoadhesion and PP uptake, microparticles labelled with fluorescein isothiocyanate (FITC) were prepared by spray-drying technique and crosslinking reactions with calcium ions and chitosan (CS), in vitro characterized and assayed by an ex vivo method. Microparticles showed a size less then 3 microm, an antibiotic loading level of 11.86 +/- 0.70%, w/w, a sustained drug release behaviour in simulated gastro-intestinal (GI) fluids and a preserved biological activity throughout the manufacture. The ex vivo study was performed by a perfusion method on intestinal tracts of just sacrificed adult rats. The recovered samples were analysed by epifluorescence microscope for mucoadhesion and PP uptake and by microbiological analysis for antibiotic activity preservation, providing evidence of mucoadhesion at the level of both PP and non-PP epithelium, uptake by PP and PMB microbiological activity in PP tissue. Furthermore, the study revealed the involvement of transport pathways across villous enterocytes.
Coppi
Gilberto
G
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41100, Modena, Italy. coppi.gilberto@unimore.it
Sala
Nicoletta
N
Bondi
Moreno
M
Sergi
Santo
S
Iannuccelli
Valentina
V
D000284:Administration, Oral; D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010316:Particle Size; D010477:Perfusion; D011112:Polymyxin B / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000464:Alginates; D000900:Anti-Bacterial Agents; D005079:Excipients; D005456:Fluorescent Dyes; D016650:Fluorescein-5-isothiocyanate; D011112:Polymyxin B