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  • Title: Toxicity and gut associated lymphoid tissue translocation of polymyxin B orally administered by alginate/chitosan microparticles in rats.
    Author: Coppi G, Bondi M, Coppi A, Rossi T, Sergi S, Iannuccelli V.
    Journal: J Pharm Pharmacol; 2008 Jan; 60(1):21-6. PubMed ID: 18088501.
    Abstract:
    Fluorescent calcium alginate/chitosan microparticles, prepared using a spray-drying technique followed by crosslinking reactions with calcium ions and chitosan, were assayed in-vivo for polymyxin B (PMB) oral toxicity, uptake by Peyer's patches and PMB oral absorption. A single PMB dose (300 mg kg(-1)), loaded in microparticles or dissolved in water, was administered to rats by oral gavage under fasted and fed conditions. By monitoring incidence of mortality, animal behaviour, clinical signs and abnormality in several organs, PMB in water solution was found lethal at a dose lower than the LD50 (790 mg kg(-1)) in the fasted state and toxic for the gastrointestinal tract in the fed state. However, no signs of acute toxicity at the level of the gastrointestinal tract were observed when animals were administered PMB loaded in microparticles under fasted and fed conditions. A lower PMB dose (125 mg kg(-1)), loaded in microparticles or dissolved in water, was given to rats in a fed state to determine PMB levels in Peyer's patches, urine and serum as well as to detect the loaded microparticles inside Peyer's patches for three days after dosing. Abnormalities were observed at gut level only when PMB was dosed in a water solution. Detectable antibiotic levels in Peyer's patches and urine as well as more constant PMB serum concentrations were provided by dosing PMB loaded in microparticles. Therefore, the use of alginate/chitosan microparticles to target the lymphatic system could improve safety when administering PMB orally.
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