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[Lymphatic targeting study of pingyangmycin-activated carbon nanoparticles treating oral cancer lymph node
Ming-Lei Sun1, Wei-Hong Xie, Chang-Mei Wang
1Dept. of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Objective:
To investigate the drug distribution in tissues of cervical lymph node metastasis mice model after submucosa adjacent cancer injection of pingyangmycin-activated carbon nanoparticles (PYM-CH-NP) and evaluate the lymph targeting effect of PYM-CH-NP.
Methods:
Pingyangmycin (PYM) was radiolabeled with 125I by modified the chloramine T method. Cervical lymph node metastasis mice model was established by buccal submucosa inoculation of a high lymph metastasis cell line U14 cancer cell. 360 mice models burdened with cervical lymph metastasis were randomly divided into 3 groups. PYM group was treated with PYM water solution, PYM-CH-NP group was treated with PYM-CH-NP. Negative control group was injected with activated carbon nanoparticles. PYM-CH-NP and pingyangmycin water solution were injected in pericancer submucosa of the mice respectively. The radioactivity of drug in blood, heart, liver, spleen, lung, kidney and cervical lymph node were measured after 0.5, 1, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168 h administration. The radioactivity of each samples per unit weight were calculated. The selectivity index (SI) and targeting index (TI) of drug were calculated.
Results:
The radioactivity of drug in cervical lymph node of PYM-CH-NP group was much higher than PYM group in each time point (P < 0.001), whereas the blood, heart, liver, spleen, lung and kidney uptake of pingyangmycin was greatly decreased in PYM-CH-NP group after 4 h administration (P < 0.001). The SI value of PYM group at each time point was less than 1. While the minimum SI and TI value of PYM-CH-NP was 1.793 and 1.562, the maximum value reached to 68.126 and 14.623 after 72 h administration.
Conclusion:
PYM-CH-NP can increase drug dosage in metastasized cervical lymph nodes, and decrease drug dosage of other organs. So better therapeutic outcome and little adverse reaction may be achieved for lymph node metastasis.
