N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride nanoparticle as a novel delivery system for Parathyroid Hormone-Related Protein 1-34

被引:35
作者
Zhao, Sheng-hao [1 ]
Wu, Xiao-ting [2 ]
Guo, Wei-chun [1 ]
Du, Yu-min [2 ]
Yu, Ling [1 ]
Tang, Jin [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Orthoped, Wuhan 430060, Peoples R China
[2] Wuhan Univ, Coll Resource & Environm Sci, Dept Environm Sci, Wuhan 430097, Peoples R China
关键词
PTHrP1-34; Chitosan; EPTAC; HTCC; Nanoparticles; DRUGS; ALGINATE; AGENT; CELLS; RATS;
D O I
10.1016/j.ijpharm.2010.04.034
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Chitosan (CS) and epoxy propyl trimethyl ammonium chloride (EPTAC) were used to prepare the water-soluble N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC). HTCC and sodium tripolyphosphate (TPP) were mixed to form HTCC nanoparticles based on ionic gelation. Parathyroid Hormone-Related Protein 1-34 (PTHrP1-34) was incorporated into the HTCC nanoparticles. The particle size and morphology of nanoparticles were determined by transmission electron microscopy (TEM). HTCC/PTHrP1-34 nanoparticles were 100-180 nm in size and their encapsulation efficiency and loading capacity were related to HTCC concentration, TPP concentration and initial concentration of PTHrP1-34. Relatively optimum encapsulation efficiency (78.4%) and loading capacity (13.7%) of PTHrP1-34 is achieved, and the in vitro release profile of PTHrP1-34 from nanoparticles has an initial burst, which is followed up by a slow release phase. These studies showed that HTCC/PTHrP1-34 nanoparticles are suitable for the treatment of osteoporosis, because of their slow-continuous-release properties, and the relevant in vivo experiments and clinical trials should be further studied. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:268 / 272
页数:5
相关论文
共 29 条
[1]   Protein encapsulation in biodegradable amphiphilic microspheres [J].
Bouillot, P ;
Ubrich, N ;
Sommer, F ;
Duc, TM ;
Loeffler, JP ;
Dellacherie, E .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1999, 181 (02) :159-172
[2]   Impact of the mitogen-activated protein kinase pathway on parathyroid hormone-related protein actions in osteoblasts [J].
Chen, C ;
Koh, AJ ;
Datta, NS ;
Zhang, J ;
Keller, ET ;
Xiao, GZ ;
Franceschi, RT ;
D'Silva, NJ ;
McCauley, LK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (28) :29121-29129
[3]  
Clark MA, 2001, VACCINE, V20, P208
[4]   Natural polymers for gene delivery and tissue engineering [J].
Dang, Jiyoung M. ;
Leong, Kam W. .
ADVANCED DRUG DELIVERY REVIEWS, 2006, 58 (04) :487-499
[5]   Effects of alginate inclusion on the vector properties of chitosan-based nanoparticles [J].
Douglas, Kimberly L. ;
Piecirillo, Ciriaco A. ;
Tabrizian, Maryam .
JOURNAL OF CONTROLLED RELEASE, 2006, 115 (03) :354-361
[6]   Polymeric nanoparticles for oral delivery of drugs and vaccines:: A critical evaluation of in vivo studies [J].
Galindo-Rodríguez, SA ;
Allémann, E ;
Fessi, H ;
Doelker, E .
CRITICAL REVIEWS IN THERAPEUTIC DRUG CARRIER SYSTEMS, 2005, 22 (05) :419-463
[7]   Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - a review [J].
George, Meera ;
Abraham, T. Emilia .
JOURNAL OF CONTROLLED RELEASE, 2006, 114 (01) :1-14
[8]   BIODEGRADABLE LONG-CIRCULATING POLYMERIC NANOSPHERES [J].
GREF, R ;
MINAMITAKE, Y ;
PERACCHIA, MT ;
TRUBETSKOY, V ;
TORCHILIN, V ;
LANGER, R .
SCIENCE, 1994, 263 (5153) :1600-1603
[9]   Chitosan-based gastrointestinal delivery systems [J].
Hejazi, R ;
Amiji, M .
JOURNAL OF CONTROLLED RELEASE, 2003, 89 (02) :151-165
[10]   Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis [J].
Horwitz, MJ ;
Tedesco, MB ;
Gundberg, C ;
Garcia-Ocana, A ;
Stewart, AF .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (02) :569-575