Lipid-based microtubular drug delivery vehicles

被引:72
作者
Meilander, NJ
Yu, XJ
Ziats, NP
Bellamkonda, RV [1 ]
机构
[1] Case Western Reserve Univ, Dept Biomed Engn, Biomat Cell & Tissue Engn Lab, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA
基金
美国国家科学基金会;
关键词
sustained release; self-assembly; rodent implantation model; NGF bioassay; protein delivery;
D O I
10.1016/S0168-3659(01)00214-0
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Lipid microtubules that self-assemble from a diacetylenic lipid are suitable structures for the sustained release of bioactive agents. Microtubules were loaded with agents under aqueous conditions and embedded in an agarose hydrogel for localization at areas of interest. Protein release from our microtubule-hydrogel delivery system was characterized in vitro, and in vivo biocompatibility was examined. The influences of protein molecular weight and initial loading concentration on release profile were evaluated by releasing test proteins myoglobin, albumin, and thyroglobulin. Protein molecular weight inversely affected the release rate, and loading with a higher protein concentration increased the mass but not the percent of initially loaded protein released daily. Preservation of protein activity was demonstrated by the ability of a neurotrophic factor released from the delivery system to induce neurite extension in PC12 cells. Bovine aortic smooth muscle cells co-cultured with the microtubule-hydrogel system showed no evidence of cytotoxicity and proliferated in the presence of the microtubules. Subcutaneous implantation of microtubules in rodents revealed no significant inflammatory response after 10 days. Our microtubule-hydrogel system is useful for applications where sustained release without contact between agent and organic solvents is desired. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:141 / 152
页数:12
相关论文
共 37 条
[1]   Liposomes - Opportunities in drug delivery [J].
Allen, TM .
DRUGS, 1997, 54 (Suppl 4) :8-14
[2]  
ANDERSON JM, 1994, EUR J PHARM BIOPHARM, V40, P1
[3]   Host response to tissue engineered devices [J].
Babensee, JE ;
Anderson, JM ;
McIntire, LV ;
Mikos, AG .
ADVANCED DRUG DELIVERY REVIEWS, 1998, 33 (1-2) :111-139
[4]   HYDROGEL-BASED 3-DIMENSIONAL MATRIX FOR NEURAL CELLS [J].
BELLAMKONDA, R ;
RANIERI, JP ;
BOUCHE, N ;
AEBISCHER, P .
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1995, 29 (05) :663-671
[5]  
Bhattacharjya S, 1997, PROTEINS, V29, P492, DOI 10.1002/(SICI)1097-0134(199712)29:4<492::AID-PROT9>3.0.CO
[6]  
2-A
[7]  
Cleek RL, 1997, J BIOMED MATER RES, V35, P525, DOI 10.1002/(SICI)1097-4636(19970615)35:4<525::AID-JBM12>3.0.CO
[8]  
2-A
[9]  
Cleland J L, 1997, Pharm Biotechnol, V10, P1
[10]   INTERACTIONS OF SUGARS WITH MEMBRANES [J].
CROWE, JH ;
CROWE, LM ;
CARPENTER, JF ;
RUDOLPH, AS ;
WISTROM, CA ;
SPARGO, BJ ;
ANCHORDOGUY, TJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1988, 947 (02) :367-384