Document Detail

Removal of chloroform from biodegradable therapeutic microspheres by radiolysis.
MedLine Citation:
PMID:  16549282     Owner:  NLM     Status:  MEDLINE    
Radioactive holmium-166 loaded poly(l-lactic acid) microspheres are promising systems for the treatment of liver malignancies. These microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method using chloroform. After preparation the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. It was observed that relatively large amounts of residual chloroform (1000-6000 ppm) remained in the microspheres before neutron irradiation. Since it is known that chloroform is susceptible for high-energy radiation, we investigated whether neutron and gamma irradiation could result in the removal of residual chloroform in HoAcAc-loaded and placebo PLLA-MS by radiolysis. To investigate this, microspheres with relatively high and low amounts of residual chloroform were subjected to irradiation. The effect of irradiation on the residual chloroform levels as well as other microsphere characteristics (morphology, size, crystallinity, molecular weight of PLLA and degradation products) were evaluated. No chloroform in the microspheres could be detected after neutron irradiation. This was also seen for gamma irradiation at a dose of 200 kGy phosgene, which can be formed as the result of radiolysis of chloroform, was not detected with gas chromatography-mass spectrometry (GC-MS). A precipitation titration showed that radiolysis of chloroform resulted in the formation of chloride. Gel permeation chromatography and differential scanning calorimetry showed a decrease in molecular weight of PLLA and crystallinity, respectively. However, no differences were observed between irradiated microsphere samples with high and low initial amounts of chloroform. In conclusion, this study demonstrates that neutron and gamma irradiation results in the removal of residual chloroform in PLLA-microspheres.
S W Zielhuis; J F W Nijsen; L Dorland; G C Krijger; A D van Het Schip; W E Hennink
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-20
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  315     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-15     Completed Date:  2006-12-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  67-74     Citation Subset:  IM    
Department of Nuclear Medicine, University Medical Center, Utrecht, The Netherlands.
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MeSH Terms
Biodegradation, Environmental
Chloroform / radiation effects*
Drug Contamination / prevention & control,  statistics & numerical data*
Gamma Rays
Lactic Acid
Molecular Weight
Reg. No./Substance:
0/Polymers; 0/Radioisotopes; 26100-51-6/poly(lactic acid); 50-21-5/Lactic Acid; 67-66-3/Chloroform; 7440-60-0/Holmium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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