Abstract:
:Although PEGylated TNF-related apoptosis-inducing ligand (PEG-TRAIL) has good tumor cell specificity and stability, its therapeutic potential is restricted by the development of tumor cell resistance. The purpose of this study was to develop an effective combination therapy with sustained biological activity based on microspheres. Doxorubicin (DOX), PEG-TRAIL, and DOX plus PEG-TRAIL (dual agent) were microencapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres using a double-emulsion solvent extraction method. Prepared dual agent microspheres showed the encapsulation efficiency 69.4 ± 2.3 for DOX and 87.7 ± 2.9% for PEG-TRAIL. Potential anti-tumor efficacy of this system was investigated in vitro and in vivo in a human colon cancer (HCT116) and in a human prostate cancer (PC-3). DOX and PEG-TRAIL release from dual agent microspheres were biologically active and significantly inhibited the TRAIL-sensitive HCT116 and resistant PC-3 cells in vitro. Dual agent microspheres simultaneous delivery of DOX and PEG-TRAIL was superior to all other DOX or PEG-TRAIL microspheres in vivo. A single local injection of PLGA microspheres loaded with low amounts of DOX, PEG-TRAIL, or dual agent resulted in 14.8, 30.2, and 63.6% reductions in HCT116 tumor volume and 20.4, 14.2, and 67.7% reductions in PC-3 tumor volume at 35 days. Our findings show that dual agent microspheres offer a promising means of delivering DOX and PEG-TRAIL to tumor sites.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Jiang HH,Kim TH,Lee S,Chen X,Youn YS,Lee KCdoi
10.1016/j.biomaterials.2011.07.051subject
Has Abstractpub_date
2011-11-01 00:00:00pages
8529-37issue
33eissn
0142-9612issn
1878-5905pii
S0142-9612(11)00834-9journal_volume
32pub_type
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