Synthesis and Characterization of PEGylated Calcium Phosphate Nanoparticles for Oral Insulin Delivery

被引:55
作者
Ramachandran, Rulkmani [1 ]
Paul, Willi [2 ]
Sharma, Chandra P. [2 ]
机构
[1] SASTRA Deemed Univ, Sch Chem & Biotechnol, Thanjavur 613402, Tamil Nadu, India
[2] Sree Chitra Tirunal Inst Med Sci & Technol, Biomed Technol Wing, Div Biosurface Technol, Thiruvananthapuram 695012, Kerala, India
关键词
calcium phosphate; nanoparticles; PEGylation; oral insulin; PROTEIN; MICROSPHERES; BIOADHESION; PARTICLES;
D O I
10.1002/jbm.b.31241
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The inconvenience of subcutaneous insulin delivery leads to low patient compliance with the dosage regimens. The most desirable form of administration seems to be through the oral route. This work investigates the utility of PEGylated calcium phosphate nanoparticles as oral carriers for insulin. Calcium phosphate nanoparticles (Cap) with an average particle size of 47.9 nm(D50) were synthesized and surface modified by conjugating it with poly(ethylene glycol) (PEG). These modified nanoparticles were having a near zero zeta potential. Protection of insulin from the gastric environment has been achieved by coating the nanoparticles with a pH sensitive polymer that will dissolve in the mildly alkaline pH environment of the intestine. The release profiles of coated nanoparticles exhibited negligible release in acidic (gastric) pH, i.e., only 2% for CaP and 6.5% for PEGylated CaP. However, a sustained release of insulin was observed at neutral (intestinal) pH for over 8 h. The conformation of the released insulin, studied using circular dichroism, was unaltered when compared with native insulin. The released insulin was also stable as it was studied using dynamic light scattering. Radioimmunoassay was performed and the immunoreactivity of the released insulin was found to be intact. These results suggest PEGylated calcium phosphate nanoparticles as an excellent carrier system for insulin toward the development of an oral insulin delivery system. (c) 2008 Wiley Periodical, Inc. J Biomed Mater Res Part B: Appl Biomater 88B: 41-48, 2009
引用
收藏
页码:41 / 48
页数:8
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