Starch microspheres induce pulsatile delivery of drugs and peptides across the epithelial barrier by reversible separation of the tight junctions.
Non-parenteral administration of peptide drugs is prevented by the limited permeability of the epithelia lining the mucosal tissues. As a new approach to non-parenteral delivery, degradable starch microspheres (dsm) were coated with insulin and administered to the mucosal side of monolayers of human intestinal epithelial (Caco-2) cells in vitro. The microspheres induced a pulsed delivery of insulin across the epithelium that lasted for 1-2 h. The pulsed delivery correlated with a reversible appearance of focal dilatations in the tight junctions between the epithelial cells, indicating that dsm enhance the delivery of insulin by the paracellular route. These results provide an explanation for the previously observed absorption enhancing properties of dsm.
Björk
E
E
Dept. of Pharmaceutics, Uppsala University, Sweden.
Isaksson
U
U
Edman
P
P
Artursson
P
P
D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D008353:Mannitol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008863:Microspheres; D010539:Permeability / Q000187:drug effects; D011673:Pulsatile Flow / Q000187:drug effects; D013213:Starch / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007328:Insulin; D008353:Mannitol; D013213:Starch