pH-sensitive and mucoadhesive thiolated Eudragit-coated chitosan microspheres.
The aim of this study was using Eudragit-cysteine conjugate to coat on chitosan microspheres (CMs) for developing an oral protein drug delivery system, having mucoadhesive and pH-sensitive property. Bovine serum albumin (BSA) as a protein model drug was loaded in thiolated Eudragit-coated CMs (TECMs) to study the release character of the delivery system. After thiolated Eudragit coating, it was found that the release rate of BSA from BSA-loaded TECMs was observably suppressed at pH 2.0 PBS solution, while at pH 7.4 PBS solution the BSA can be sustainingly released for several hours. The structural integrity of BSA released from BSA-loaded TECMs was guaranteed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD) spectroscopy. The mucoadhesive property of TECMs was evaluated and compared with CMs and Eudragit-coated chitosan microspheres (ECMs). It was confirmed that after coating thiolated Eudragit, the percentage of TECMs remained on the isolated porcine intestinal mucosa surface was significantly higher than those of CMs and ECMs. Likewise, gamma camera imaging of Tc-99m labeled microsphere distribution in rats after oral administration also suggested that TECMs had comparatively stronger mucoadhesive characters. Therefore, our results indicated that TECMs have potentials to be an oral protein drug carrier.
Quan
Ji-Shan
JS
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.
Jiang
Hu-Lin
HL
Kim
Eun-Mi
EM
Jeong
Hwan-Jeong
HJ
Choi
Yoon-Jaie
YJ
Guo
Ding-Ding
DD
Yoo
Mi-Kyong
MK
Lee
Hong-Gu
HG
Cho
Chong-Su
CS
D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D048271:Chitosan / Q000737:chemistry*; D002942:Circular Dichroism; D004337:Drug Carriers / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D008863:Microspheres; D011109:Polymethacrylic Acids / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013552:Swine; D014018:Tissue Distribution
D004337:Drug Carriers; D011109:Polymethacrylic Acids; D013438:Sulfhydryl Compounds; C038300:methylmethacrylate-methacrylic acid copolymer; D012710:Serum Albumin, Bovine; D048271:Chitosan