Particle size and temperature effect on the physical stability of PLGA nanospheres and microspheres containing Bodipy

被引:59
作者
De, SJ
Robinson, DH
机构
[1] Dept Pharmaceut Sci, Omaha, NE 68198 USA
[2] Ohio No Univ, Coll Pharm, Ada, OH 45810 USA
关键词
nanospheres; microspheres; Bodipy; temperature; aggregation;
D O I
10.1208/pt050453
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
The purpose of this study was to investigate the effect of particle size, storage temperature, and duration of storage on the physical stability and morphology of polylactic-co-glycolic acid (PLGA) nanospheres and microspheres. PLGA nanospheres and microspheres containing the fluorescent dye, Bodipy, were prepared in varying sizes by controlling the method and degree of agitation during the emulsification phase of preparation. Mean diameters of the particles were measured by dynamic light scattering. To evaluate the effect of storage temperature and duration of storage on the extent of aggregation, nanospheres and microspheres were stored at 4degreesC, 25degreesC, 37degreesC, and 50degreesC for 6 days and then monitored using both confocal and scanning electron microscopy. The mean +/- SD diameters of PLGA particles containing Bodipy were: 266.9 +/- 2.8, 351.6 +/- 1.8, 988.8 +/- 14.1, and 1865.9 +/- 67.0 nm. The extent of aggregation of the particulate delivery system decreased as the mean diameter increased, and increased as the storage temperature increased. The maximum extent of aggregation was observed with the smallest (266 nm) nanospheres. Microspheres did not aggregate. The aggregation of nanospheres was significantly reduced by introducing an additional evaporation step during preparation, suggesting that migration of residual dichloromethane from within the nanospheres may have dissolved the PLGA on the surface. The extent of aggregation of nanospheres increased as the temperature was increased from 4degreesC to 50degreesC, and decreased as particle size increased. To avoid aggregation, PLGA nanospheres should be stored at 4degreesC.
引用
收藏
页数:7
相关论文
共 23 条
[1]
Effect of blending calcium compounds on hydrolytic degradation of poly(DL-lactic acid-co-glycolic acid) [J].
Ara, M ;
Watanabe, M ;
Imai, Y .
BIOMATERIALS, 2002, 23 (12) :2479-2483
[2]
Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide) methoxypoly(ethyleneglycol) copolymers related to their application in controlled drug delivery [J].
Beletsi, A ;
Leontiadis, L ;
Klepetsanis, P ;
Ithakissios, DS ;
Avgoustakis, K .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1999, 182 (02) :187-197
[3]
Polymer relationships during preparation of chitosan-alginate and poly-l-lysine-alginate nanospheres [J].
De, SJ ;
Robinson, D .
JOURNAL OF CONTROLLED RELEASE, 2003, 89 (01) :101-112
[4]
Determination of water-soluble acid distribution in poly(lactide-co-glycolide) [J].
Ding, AG ;
Schwendeman, SP .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2004, 93 (02) :322-331
[5]
Feng S. S., 2000, Annals Academy of Medicine Singapore, V29, P633
[6]
Effects of emulsifiers on the controlled release of paclitaxel (Taxol®) from nanospheres of biodegradable polymers [J].
Feng, SS ;
Huang, GF .
JOURNAL OF CONTROLLED RELEASE, 2001, 71 (01) :53-69
[7]
Gaspar MM, 1998, J CONTROL RELEASE, V52, P53
[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]
Kranz H, 2000, J PHARM SCI-US, V89, P1558
[10]
Lu L, 1999, J BIOMED MATER RES, V46, P236, DOI 10.1002/(SICI)1097-4636(199908)46:2<236::AID-JBM13>3.0.CO