The targeting to Gut Associated Lymphoid Tissue (GALT) by uptake through M cells in Peyer's patches (PP) represents a possible strategy to improve the oral absorption of Polymyxin B (PMB), polypeptidic antibiotic with poor bioavailability after oral administration and systemic toxicity. The uptake by PP is feasible for an inert carrier with proper dimensions. Therefore, crosslinked calcium alginate/chitosan unfluorescent and fluorescent (FITC) microparticles loaded with PMB were prepared by spray-drying process and interfacial crosslinking process. The microparticles were in vitro characterised for PMB/alginate interaction, size, PMB content and PMB release (1). The ex vivo assay demonstrated the effective microparticle uptake by PP and PMB antimicrobial activity inside PP (2). Moreover, fluorescent microparticles were assayed in vivo by animal model, male rats Wistar, in accordance with the European Community regulations (CEE Council 89/609: Italian D.L.vo. 22-1-92 n. 116), in order to detect PMB toxicity and bioavailability (3, 4). The toxicity evaluation was performed following a single oral administration of PMB-loaded microparticles in comparison with unloaded microparticles and pure PMB. The toxicity effects were evaluated by the observation of animal behaviour, clinical signs and macroscopic abnormalities after animal sacrifice. The PMB bioavailability from microparticles was assayed administering, by oral gavage, to three groups of animals an aqueous suspension of the fluorescent PMB-loaded microparticles, in comparison with unloaded microparticles and PMB water solution. Six animals for each group were sacrificed after 24 h, 48 h and 72 h. Urine, blood and intestine samples were collected, whereas other organs were morphologically observed. The PMB levels in urine and serum, from blood, were determined by microbiological assay. The study revealed a strong toxicity reduction, a more constant serum level for PMB dosed by the microparticle system in comparison with PMB solution and the microparticle presence inside PP. Therefore, calcium alginate/chitosan microparticles could offer advantages in a perspective of an oral therapy with polymyxin B.
Alginate microparticles for Polymyxin B targeting to lymphatic system / Iannuccelli, V.. - (2007). (Intervento presentato al convegno Research to Business - la ricerca rinnova l'impresa. Innovative nano and microparticles for drug bioavailability optimization tenutosi a Bologna nel 4 maggio 2007).