Cellular uptake and toxicity of microparticles in a perspective of polymyxin B oral administration.
Alginate/chitosan microparticles with a mean size less than 1 microm, designed in a previous work for the targeting of polymyxin B to M-cells and, then, to the lymphatic system, were assayed for transport ability by enterocytes. Caco-2 cell monolayer model, combined with confocal microscopy, showed that microparticles were endocytosed by the cells through an energy-dependent process, being the process saturable at 6 h incubation. Furthermore, microparticles maintained the biological activity of the antibiotic and decreased the antibiotic cytotoxicity against Vero cell cultures. Therefore, simultaneous pathways via both M-cells and enterocytes could be proposed for such a microparticulate carrier.
Coppi
G
G
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, via Campi, 183-41100 Modena, Italy. gilberto.coppi@unimore.it
Montanari
M
M
Rossi
T
T
Bondi
M
M
Iannuccelli
V
V
D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity; D002522:Chlorocebus aethiops; D004337:Drug Carriers; D004705:Endocytosis; D020895:Enterocytes / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry / Q000633:toxicity; D006603:Hexuronic Acids / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010316:Particle Size; D011112:Polymyxin B / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014709:Vero Cells
D000464:Alginates; D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D048271:Chitosan; D011112:Polymyxin B