OBJECTIVETo assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs.

METHODSTwelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application.

RESULTSNo local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28∓0.33 ng/mL), as compared to 4 h in the control group (42.46∓0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group.

CONCLUSIONPOD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.