Oral delivery of insulin by using surface coating liposomes - Improvement of stability of insulin in GI tract

The potency of surface coating liposomes with some materials was investigated for oral delivery of peptide drugs. In vitro release of insulin, a model peptide, from liposomes in the bile salts solution was markedly reduced by coating the surface with the sugar chain portion of mucin (Mucin-Lip) or polyethyleneglycol (PEG-Lip). Encapsulation of insulin into Mucin-Lip and PEG-Lip completely suppressed the degradation of insulin in the intestinal fluid, whereas uncoated liposomes suppressed it only partially. These results demonstrated that surface coating liposomes with PEG or mucin gained resistance against digestion by bile salts and increased the stability in the GI tract. When insulin was orally administered to rats as either a solution or non-charged liposome ((N)-Lip), no hypoglycemic effect was observed. Administration of insulin encapsulated in positively charged liposome ((+)-Lip) caused the rapid decrease in the plasma glucose level which recovered to the control level within 3 h. In contrast, PEG-Lip and Mucin-Lip caused a gradual decrease in the glucose level after administration. The hypoglycemic effect by PEG-Lip lasted for much longer duration than that of uncoated liposomes. The slow release of insulin from the surface coating liposomes achieved the longer duration of oral hypoglycemic activity. Consequently, the surface coating should be the potential way to add desirable functions to the liposome for oral drug delivery. (C) 1997 Elsevier Science B.V.