Mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric chains in the gastrointestinal tract.
The mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric chains in the gastrointestinal (GI) tract was investigated in rats. Radiolabeled nanoparticles were synthesized by adding hydrophobic 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine in the final process of nanoparticle preparation. The radioiodonated diazirine seemed to be incorporated in the hydrophobic polystyrene core of nanoparticles. The incorporation rate was less than 10%, irrespective of nanoparticle type. The diazirine incorporated in nanoparticles exhibited little leakage from them even though they were mixed with a solution corresponding to GI juice. The change in blood ionized calcium concentration after oral administration of salmon calcitonin (sCT) with nanoparticles showed that the in vivo enhancement of sCT absorption by radiolabeled nanoparticles was the same as that by non-labeled nanoparticles. The GI transit rates of nanoparticles having surface poly(N-isopropylacrylamide), poly(vinylamine) and poly(methacrylic acid) chains, which can improve sCT absorption, were slower than that of nanoparticles covered by poly(N-vinylacetamide), which does not enhance sCT absorption at all. These slow transit rates were probably the result of mucoadhesion of nanoparticles. The strength of mucoadhesion depended on the structure of the hydrophilic polymeric chains on the nanoparticle surface. The mucoadhesion of poly(N-isopropylacrylamide) nanoparticles, which most strongly enhanced sCT absorption, was stronger than that of ionic nanoparticles, and poly(N-vinylacetamide) nanoparticles probably did not adhere to the GI mucosa. These findings demonstrated that there is a good correlation between mucoadhesion and enhancement of sCT absorption.
Sakuma
S
S
Pharmaceutical Formulation Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. sakumv8j@daiichipharm.co.jp
Sudo
R
R
Suzuki
N
N
Kikuchi
H
H
Akashi
M
M
Hayashi
M
M
D000700:Analgesics / Q000378:metabolism*; D000758:Anesthesia; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003978:Diazomethane / Q000737:chemistry; D004068:Digestive System Physiological Phenomena; D005772:Gastrointestinal Transit; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D000267:Tissue Adhesions / Q000473:pathology*
D000700:Analgesics; D011108:Polymers; D011137:Polystyrenes; D003978:Diazomethane; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium