In vitro and in vivo evaluation of the effects of PLA microparticle crystallinity on cellular response

被引:28
作者
Biggs, DL
Lengsfeld, CS
Hybertson, BM
Ng, KY
Manning, MC
Randolph, TW
机构
[1] Univ Colorado, Engn Ctr, Ctr Pharmaceut Biotechnol, Dept Chem Engn, Boulder, CO 80309 USA
[2] Univ Denver, Dept Engn, Denver, CO 80262 USA
[3] Univ Colorado, Hlth Sci Ctr, Webb Waring Inst Canc Aging & Antioxidant Res, Denver, CO 80262 USA
[4] Univ Colorado, Hlth Sci Ctr, Sch Med, Denver, CO 80262 USA
[5] Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80262 USA
关键词
poly(L-lactic acid); microparticles; crystallinity; alveolar macrophages; biocompatibility;
D O I
10.1016/S0168-3659(03)00325-0
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Previous research suggests that crystallinity of poly(L-lactide) P(L)LA microparticles can influence surface free energy, which in turn might influence biocompatibility. This work studies the cellular response to P(L)LA microparticles of different crystallinity both in vitro and in vivo. Following incubation with P(L)LA microparticles, the in vitro production of reactive oxygen intermediates (ROI) was measured as a market of cellular response. In both fluorescence and chemiluminescence experiments to measure ROI, a small effect of microparticle crystallinity on NR8383 AM response was observed. Microparticles of higher crystallinity elicited a smaller inflammatory response compared to lower crystallinity particles. Compared to the elevated inflammatory response induced by zymosan, the response to all P(L)LA microparticles tested was practically negligible. Results from in vivo experiments further supported conclusions that P(L)LA microparticles elicit minimal inflammatory response. Following acute exposure to P(L)LA microparticles in guinea-pig lungs, the inflammatory response was not significantly different from the response observed when sterile saline was administered. In contrast to the in vitro experiments, there were not apparent differences in cellular responses to microparticles of different crystallinity. (C) 2003 Published by Elsevier B.V.
引用
收藏
页码:147 / 161
页数:15
相关论文
共 70 条
[1]  
ADAMSON AW, 1967, PHYSICAL CHEM SURFAC
[2]   THE MECHANISMS OF OXIDATIVE-DEGRADATION OF BIOMEDICAL POLYMERS BY FREE-RADICALS [J].
ALI, SAM ;
DOHERTY, PJ ;
WILLIAMS, DF .
JOURNAL OF APPLIED POLYMER SCIENCE, 1994, 51 (08) :1389-1398
[3]   MOLECULAR BIOINTERACTIONS OF BIOMEDICAL POLYMERS WITH EXTRACELLULAR EXUDATE AND INFLAMMATORY CELLS AND THEIR EFFECTS ON THE BIOCOMPATIBILITY, IN-VIVO [J].
ALI, SAM ;
DOHERTY, PJ ;
WILLIAMS, DF .
BIOMATERIALS, 1994, 15 (10) :779-785
[4]   Poly-(D,L-lactic acid) microspheres incorporating histological dyes for intra-pulmonary histopathological investigations [J].
Armstrong, DJ ;
Elliott, PNC ;
Ford, JL ;
Gadsdon, D ;
Mccarthy, GP ;
Rostron, C ;
Worsley, MD .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1996, 48 (03) :258-262
[5]  
AUGER MJ, 1992, NATURAL IMMUNE SYSTE, P3
[6]   THE RESPIRATORY BURST OF PHAGOCYTES [J].
BABIOR, BM .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 73 (03) :599-601
[7]   Is the neutrophil reactive oxygen species production measured by luminol and lucigenin chemiluminescence intra or extracellular?: Comparison with DCFH-DA flow cytometry and cytochrome c reduction [J].
Caldefie-Chézet, F ;
Walrand, S ;
Moinard, C ;
Tridon, A ;
Chassagne, J ;
Vasson, MP .
CLINICA CHIMICA ACTA, 2002, 319 (01) :9-17
[8]  
Champiat D., 1993, P15
[9]   Role of crystallinity in retention of polymer particle morphology in the presence of compressed carbon dioxide [J].
Connon, CS ;
Falk, RF ;
Randolph, TW .
MACROMOLECULES, 1999, 32 (06) :1890-1896
[10]  
Corkery K, 2000, Respir Care, V45, P831