羧基化碳纳米管负载鬼臼毒素的制备及透皮性能研究

Preparation of Carboxylated Multi-Walled Carbon Nanotubes Loaded with Podophyllotoxin and Their Transdermal Penetration

目的研究羧基化碳纳米管负载鬼臼毒素(PPT-CNTs-COOH)的制备以及体外透皮的特性。方法采用冷冻球磨法制备PPT-CNTs-COOH;采用红外、紫外、X-衍射、热重分析对其进行表征,并采用HPLC测定负载物中鬼臼毒素的含量;采用体外Franze扩散池法测定药物透皮速率;采用家兔的皮肤刺激性实验评价药物皮肤刺激性。结果 PPT-CNTs-COOH中鬼臼毒素的含量为58.0μg·mg^(-1);PPT凝胶的透皮速率为7.08μg·cm^(-2)·h^(-1),而PPT-CNTs-COOH凝胶的为3.03μg·cm^(-2)·h^(-1),PPT-CNTs-COOH凝胶的皮肤滞留量为3.04μg·cm^(-2),PPT凝胶为1.52μg·cm^(-2);PPT-CNTs-COOH凝胶涂药24 h内表现为轻度刺激性,48 h后刺激性逐渐降低,72 h后刺激性消失。结论 PPT-CNTs-COOH体外透皮具有显著缓释效果,皮肤滞留量高,利于局部透皮给药治疗。

OBJECTIVE To study the preparation of carboxylated muhi-walled carbon nanotubes loaded with podophyllotoxin （PPT-CNTs-COOH） as well as the characteristics of the in vitro transdermal penetration. METHODS PPT-CNTs-COOH was pre- pared by freezing milling method; IR, UV, XRD, and TGA were used to characterize the PPT-CNTs-COOH; HPLC method was used for determination of the content of podophyllotoxin loaded in the carboxylated multi-wailed carbon nanotubes; franze diffusion cells method was used to determine the drug transdermal penetration rate. RESULTS The IR spectrum of PPT-CNTs-COOH showed the main absorption peaks of PPT and CNTs-COOH and the peaks changed obviously. Compared with free PPT, the UV absorption peaks of PPT-CNTs-COOH changed obviously. The PPT content in the CNTs-COOH gel was 58.0μg·mg^-1 ; the transdermal penetration rate of PPT gel was 7. 08 μg·cm^-2·h^-1 and that of the PPT-CNTs-COOH gel was 3.03μg·cm^-2·h^-1 ; the skin retention of PPT- CNTs-COOH gel was 3.04μg·cm^-2, far less than the 1.52μg·cm^-2 of PPT gel. Mild irritation developed within 24 h following re- moval of the PPT-CNTs-COOH gel, and disappears after 72 h. CONCLUSION Podophyllotoxin can successfully be loaded into the carboxylated multi-wall carbon nanotubes by using the frozen ball milling method. The product has remarkable sustained release effect in vitro and high retention in skin, which is beneficial to transdermai delivery.