title: N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin.
abstract: Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13 ± 20.50 to 448.84 ± 103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing-210009, PR China.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Huang
authors.forename: Abdallah
authors.initials: A
authors.lastname: Makhlof
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001769:Blood / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018625:Microscopy, Atomic Force; D009077:Mucins / Q000737:chemistry; D010755:Organophosphates / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D055672:Static Electricity; D013499:Surface Properties; D013844:Thiazoles / Q000008:administration & dosage / Q000378:metabolism; D053835:Unilamellar Liposomes / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D050071:Bone Density Conservation Agents; D003374:Coumarins; D004337:Drug Carriers; D009077:Mucins; C118071:N-trimethyl chitosan chloride; D010755:Organophosphates; D010713:Phosphatidylcholines; D013844:Thiazoles; D053835:Unilamellar Liposomes; C517282:coumarin 6; C002290:dicetylphosphate; C028815:salmon calcitonin; D002116:Calcitonin; D048271:Chitosan; D002784:Cholesterol; C010942:1,2-distearoyllecithin; D002118:Calcium