Improved intestinal absorption of calcitonin by mucoadhesive delivery of novel pectin-liposome nanocomplexes.
Self-assembling pectin-liposome nanocomplexes (PLNs) were prepared by a simple mixing of cationic liposomes with pectin solution, in order to improve intestinal absorption of calcitonin (eCT). Both in-vitro and in-vivo evaluations for PLNs were evaluated. The results showed that average particle size of PLNs was significantly larger than that of initial cationic liposomes. The surface charges were shifted from positive to negative after mixing with pectin. The PLNs made of high degree of esterification (DE) pectin showed less negatively charged values than those made of low DE pectin. The entrapment efficiency in cationic liposomes was in the same range even if the drug loading was increased. The in-vivo mucoadhesive test of pectin by confocal laser scanning microscopy demonstrated stronger mucoadhesive properties of PLNs made of low DE pectin, compared to cationic liposomes and PLNs made of other pectins. Moreover, high intensities of a fluorescent marker could be observed throughout the small intestines (i.e. duodenum, jejunum and ileum) and remained at the site of mucoadhesion even after 6 h of administration of PLNs made of low DE pectin. The eCT-loaded PLNs demonstrated a strong pharmacological action over the eCT solution and eCT-loaded liposomes, in which an enhanced and prolonged reduction in plasma calcium concentration of rats was observed. This was attributed to the ability of pectin to adhere to the mucus layer and prolong retention in the intestinal mucosa.
Thirawong
Nartaya
N
Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000 Thailand.
Thongborisute
Jringjai
J
Takeuchi
Hirofumi
H
Sriamornsak
Pornsak
P
D000268:Adhesiveness; D000284:Administration, Oral; D000588:Amines / Q000737:chemistry; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002784:Cholesterol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005215:Fasting; D007408:Intestinal Absorption / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D008970:Molecular Weight; D009077:Mucins / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D010368:Pectins / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000588:Amines; D008081:Liposomes; D009077:Mucins; D010713:Phosphatidylcholines; D010368:Pectins; D002116:Calcitonin; D002784:Cholesterol; C010942:1,2-distearoyllecithin; C009317:stearylamine; D002118:Calcium