Preparation and lymphatic targeting study of pingyangmycin-activated charcoal nanoparticles

Abstract

Objective To explore the possibility of anticancer drug targeting to lymph metastasis using activated charcoal nanoparticles as a drug delivery carrier, the drug distribution in tissues of cervical lymph node metastasis mice model after submucosa adjacent cancer injection of pingyangmycin (PYM ) absorbed in activated charcoal nano-particles ( ACH-NP) and the lymph targeting effect of PYM-ACH-NP.Methods PYM-ACH-NP was prepared by mixed the ACH-NP + PYM + saline and shaken for 20 min. The absorbency of PYM on ACH-NP was evaluated. Cervical lymph node metastasis mice model was established by buccal submucosa implantation of a high lymph metastasis cell line U14 cancer cells (5 × 10 /L). PYM was radiolabeled with 125I by the modified chloramine T method. Thirty Kunming mice models burdened with cervical lymph metastasis were randomly divided into control group, PYM-treated group and PYM-ACH-NP-treated group. The animal in each group was injected with 0. 2 mL saline or corresponding drugs (equal to 10 mg/kg PYM) respectively. The radioactivity of PYM in blood, heart, liver, spleen, lung,kidney and cervical lymph node was detected 72 h after administration. Specific radioactivity of each sample was calculated. Results The average diameter of PYM-ACH-NP was 176 nm. The absorbency of PYM on ACH-NP was increased with the increased ratio of ACH-NP to PYM. In PYM-CH-NP group, specific radioactivity of PYM was significantly higher in cervical lymph node ( 148. 72 ± 29. 35 ) cpm/mg than in PYM group ( 10. 17 ±2. 11) cpm/mg ( P ＜0. 01 ) , meanwhile the specific radioactivity of drug in the blood, heart, liver, spleen, lung and kidney of PYM-CH-NP group was (2. 18 ±0. 39), (1. 19 ±0.21) ,(2.41 ±0.50) , (1.09 ±0.24) , (1.95 ±0.47) and (2.21 ±0.44) cpm/mg respectively, which was significantly lower than in PYM group (17. 22 ± 3. 04) , (2. 48 ± 0. 47 ), (6. 94 ± 1. 38 ), (4. 12 ±0.79), (8. 25 ±2.04), (18. 83 ±3. 89) cpm/mg. The uptake of PYM in the blood, heart, liver,spleen, lung and kidney was greatly decreased in PYM-CH-NP group (P ＜0. 01). Conclusion The activated charcoal nanoparticles has high absorbency of PYM. ACH-NP may serve as a new drug delivery carrier of PYM. Anticancer nanoparticles with the average diameter of 176 nm could deliver anticancer drug to lymph nodes metastasis specifically and decrease drug dosage of other organs. It will be promising in anticancer applications by elevating the therapeutic effect for lymph metastasis and reducing adverse reaction. Key words: Nanoparticle; Activated carbon; Pingyangmycin; Lymph metastasis