Alginate-PLL cell encapsulation system Co-entrapping PLGA-microspheres for the continuous release of anti-inflammatory drugs

被引:22
作者
Baruch, Limor
Benny, Ofra
Gilert, Ariel
Ukobnik, Marina [2 ]
Ben Itzhak, Ofer [2 ]
Machluf, Marcelle [1 ]
机构
[1] Technion Israel Inst Technol, Fac Biotechnol & Food Engn, Lab Canc Drug Delivery & Mammalian Cell Technol, IL-32000 Haifa, Israel
[2] Rambam Med Ctr, Dept Pathol, Haifa, Israel
关键词
Cell delivery device; PLGA; Drug delivery; Inflammatory response; Ibuprofen; IN-VIVO; COMPOSITE MICROCAPSULES; POLYMERIC MICROSPHERES; TUMOR-THERAPY; DELIVERY; SURVIVAL; GROWTH; MODEL; VITRO;
D O I
10.1007/s10544-009-9327-3
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
In spite of advances in cell microencapsulation technology in the past three decades, this approach still suffers from obstacles associated with its biocompatibility. We hypothesized that encapsulation system, which incorporates polymeric particles releasing anti-inflammatory drug in addition to the encapsulated cells, will result in improved biocompatibility, thus improving therapeutic efficacy. We have developed, optimized and studied a combined microencapsulation system in which Ibuprofen loaded PLGA microspheres (MS) are co-entrapped with cells. The combined system was developed and optimized in terms of Ibuprofen release profile, and the survival and proliferation of the co-encapsulated cells. The biocompatibility of the system was evaluated in vitro and in vivo. The developed system was shown to release Ibuprofen within two weeks, and support long-term cell viability. The combined system had improved the biocompatibility within the release period of Ibuprofen. All together, the coencapsulation of anti-inflammatory loaded MS along with cells offers a clear advantage in the development of effective, long lasting cell based drug delivery systems. The choice of the anti-inflammatory agent, or combination of several anti-inflammatory agents needs to be carefully optimized, as well as their release profile to achieve long-term biocompatibility.
引用
收藏
页码:1103 / 1113
页数:11
相关论文
共 35 条
[11]   DELIVERY OF RECOMBINANT GENE-PRODUCTS WITH MICROENCAPSULATED CELLS IN-VIVO [J].
CHANG, PL ;
SHEN, N ;
WESTCOTT, AJ .
HUMAN GENE THERAPY, 1993, 4 (04) :433-440
[12]   Pig islet xenotransplantation into non-human primate model [J].
Dufrane, Denis ;
Gianello, Pierre .
TRANSPLANTATION, 2008, 86 (06) :753-760
[13]   Perivascular graft heparin delivery using biodegradable polymer wraps [J].
Edelman, ER ;
Nathan, A ;
Katada, M ;
Gates, J ;
Karnovsky, MJ .
BIOMATERIALS, 2000, 21 (22) :2279-2286
[14]   Continuous release of endostatin from microencapsulated engineered cells for tumor therapy [J].
Joki, T ;
Machluf, M ;
Atala, A ;
Zhu, JH ;
Seyfried, NT ;
Dunn, IF ;
Abe, T ;
Carroll, RS ;
Black, PM .
NATURE BIOTECHNOLOGY, 2001, 19 (01) :35-39
[15]   Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering [J].
Kempen, Diederik H. R. ;
Lu, Lichun ;
Hefferan, Teresa E. ;
Creemers, Laura B. ;
Maran, Avudaiappan ;
Classic, Kelly L. ;
Dhert, Wouter J. A. ;
Yaszemski, Michael J. .
BIOMATERIALS, 2008, 29 (22) :3245-3252
[16]   MICROENCAPSULATED ISLETS AS BIOARTIFICIAL ENDOCRINE PANCREAS [J].
LIM, F ;
SUN, AM .
SCIENCE, 1980, 210 (4472) :908-910
[17]   Flt3 ligand stimulates proliferation and inhibits apoptosis of acute myeloid leukemia cells: Regulation of Bcl-2 and Bax [J].
Lisovsky, M ;
Estrov, Z ;
Zhang, X ;
Consoli, U ;
SanchezWilliams, G ;
Snell, V ;
Munker, R ;
Goodacre, A ;
Savchenko, V ;
Andreeff, M .
BLOOD, 1996, 88 (10) :3987-3997
[18]  
MACHLUF M, 2005, CELL BASED DELIVERY
[19]  
MACHLUF M, 2005, FOCUS BIOTECHNOLOGY, V2
[20]   Self-cross-linking polyelectrolyte complexes for therapeutic cell encapsulation [J].
Mazumder, M. A. Jafar ;
Shen, Feng ;
Burke, Nicholas A. D. ;
Potter, Murray A. ;
Stoever, Harald D. H. .
BIOMACROMOLECULES, 2008, 9 (09) :2292-2300