Polyethylene glycol-coated liposomes for oral delivery of recombinant human epidermal growth factor.
The present study was to investigate the feasibility of oral delivery of recombinant human epidermal growth factor (rhEGF). Polyethylene glycol (PEG)-coated liposomes containing rhEGF was prepared and evaluated for their stability and permeability in Caco-2 cells. In the animal study, we also determined plasma concentration and gastric ulcer healing effect after oral administration of rhEGF liposomes or the solution. Encapsulation of rhEGF into liposomes, suppressed the degradation in Caco-2 cell homogenate compared with the solution. The flux of rhEGF from dipalmitoylphosphatidylcholine (DPPC) liposome across Caco-2 cell monolayer from the apical to basolateral side was three times greater than that from phosphatidylcholine (PC) liposome or the solution. After oral administration of rhEGF liposomes or the solution in rats, the area under the concentration-time curve (AUC) of rhEGF increased 1.7- and 2.5-fold for PC and DPPC liposomes, respectively. The gastric ulcer healing effect was significantly increased in DPPC liposome compared with PC liposome and the solution. The enhanced curative ratio of rhEGF encapsulated into DPPC liposome may be due to the resistance to enzyme degradation, higher permeability and increased plasma AUC. Therefore, PEG-coated liposomes containing rhEGF could be used as an oral delivery formulation with enhanced encapsulation efficiency.
Li
Hong
H
College of Pharmacy, Chungbuk National University, 361-763, Chungbuk, Cheongju, South Korea.
Song
Jong Hwa
JH
Park
Jeong Sook
JS
Han
Kun
K
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001692:Biological Transport; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism*; D005240:Feasibility Studies; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008297:Male; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
D008081:Liposomes; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor