Evaluation of poly(D,L-lactide-co-glycolide) microspheres for the lung-targeting of yuanhuacine, a novel DNA topoisomerase I inhibitor.
The present study was intended to develop poly(D,L-lactide-co-glycolide) (PLGA; 50:50, 0.15 dL/g) microspheres (MS) loaded with yuanhuacine (YHC) for passive targeting in lung as well as providing a simple evaluation method for the targeting efficiency of MS. A kind of photochromic spiropyran dye was applied to label MS to clearly demonstrate the in vivo distribution characteristics through intravenous injection into mice and rabbits. Sections of 10-microm thickness from different organs were cut using a microtome, and fluorescent microscopy was used to determine the biodistribution of the MS. The average particle size of MS was 9.0 microm, and the glass transition temperature was 37-40 degrees C. In vitro, the cumulative release achieved 50.8% in 24 h. Histological sections from different organs indicated that the amount of MS in lung achieved maximum in 6 h, as about 8 times as in liver and 70 times higher than the average concentration of other organs. In vivo, MS were gradually swelled and drug concentration remained just 10% in 12 h, which would not result in long time embolization in the lung. This evaluation method supplies a simple and visualized channel in focus for the targeting efficiency of PLGA MS.
Zhang
Shixuan
S
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, People's Republic of China. zhangsx56@yahoo.com.cn
Gao
Xiujuan
X
Shen
Kaihua
K
Yang
Puwen
P
Ju
Xiulan
X
D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008863:Microspheres; D008867:Microtomy; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D014018:Tissue Distribution; D059004:Topoisomerase I Inhibitors; D044366:Transition Temperature
D004224:Diterpenes; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C029912:Yuanhuacin