Multivesicular liposomes for oral delivery of recombinant human epidermal growth factor.
The purpose of the present study was to prepare multivesicular liposomes with a high drug loading capacity and to investigate its potential applicability in the oral delivery of a peptide, human epidermal growth factor (rhEGF). The multivesicular liposomes containing rhEGF was prepared by a two-step water-in-oil-in-water double emulsification process. The loading efficiency was increased as rhEGF concentration increased from 1 to 5 mg/mL, reaching approximately 60 % at 5 mg/mL. Approximately 47% and 35% of rhEGF was released from the multivesicular liposomes within 6 h in simulated intra-gastric fluid (pH 1.2) and intra-intestinal fluid (pH 7.4), respectively. rhEGF-loaded multivesicular liposomes markedly suppressed the enzymatic degradation of the peptide in an incubation with the Caco-2 cell homogenate. However, the transport of rhEGF from the multivesicular liposomes to the basolateral side of Caco-2 cells was two times lower than that of the rhEGF in aqueous solution. The gastric ulcer healing effect of rhEGF-loaded multivesicular liposomes was significantly enhanced compared with that of rhEGF in aqueous solution; the healing effect of the liposomes was comparable to that of the cimetidine in rats. Collectively, these results indicate that rhEGF-loaded multivesicular liposomes may be used as a new strategy for the development of an oral delivery system in the treatment of peptic ulcer diseases.
Li
Hong
H
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.
An
Jun Hee
JH
Park
Jeong-Sook
JS
Han
Kun
K
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004355:Drug Stability; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D000431:Ethanol; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000138:chemical synthesis*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D013997:Time Factors
D000897:Anti-Ulcer Agents; D008081:Liposomes; D011994:Recombinant Proteins; D000431:Ethanol; D004815:Epidermal Growth Factor