[Antitumor activity of mitoxantrone-nanosphere against murine liver tumor H22].

OBJECTIVE: [corrected] To make a comparison between mitoxantrone (DHAQ) and liver targeting drug delivery system mitoxantrone-polybutylcyanoacrylate-nanosphere (DHAQ-PBCA-NS) in respect to their antitumor activity against experimental liver tumor H22 in mice. METHODS: Drugs were given intravenously on the 1st, 5th, 9th day after planting tumor respectively. Weight of tumor in mouse was determined and the results were compared with those of mitoxantrone (DHAQ). RESULTS: There was relationship of dose-effect for both DHAQ and DHAQ-PBCA-NS, and the median effective dose (ED50) of DHAQ and DHAQ-PBCA-NS was 1.04 mg/kg and 0.34 mg/kg respectively. The lethal dose to 50% of the population (LD50) of DHAQ and DHAQ-PBCA-NS i.v. in mice with the same administration schedule was 3.670 mg/kg and 4.225 mg/kg respectively. Therefore, the calculated value of therapeutic index was 3.53 for DHAQ and 12.43 for DHAQ-PBCA-NS. In addition, the antitumor activity of both drugs with different treatment schedules was reported. The results showed: the earlier the mice were treated, the higher the antitumor activity of the two drugs were seen. However, DHAQ-PBCA-NS presented higher activity than DHAQ did, when the same treatment schedule was followed. CONCLUSION: The results demonstrated that the antitumor activity of DHAQ-PBCA-NS is much higher than that of DHAQ, and DHAQ-PBCA-NS is possessed of liver targeting property.

In vivo biodistribution, anti-inflammatory, and hepatoprotective effects of liver targeting dexamethasone acetate loaded nanostructured lipid carrier system.

We aimed to evaluate whether the enhancement of the liver accumulation and anti-inflammatory activity of dexamethasone acetate (DXMA) could be achieved by incorporating it into nanostructured lipid carrier (NLCs). DXMA-NLCs were prepared using a film dispersion-ultrasonication method and characterized in terms of particle size, PDI, zeta potential, differential scanning calorimetry, drug loading capacity, encapsulation efficiency, and in vitro release. The biodistribution and pharmacokinetics of DXMA-NLCs in mice were significantly different from those of the DXMA solution (DXMA-sol). The peak concentration of DXMA-NLCs was obtained half an hour after intravenous administration. More than 55.62% of the total administrated dose was present in the liver. An increase of 2.57 fold in the area under the curve was achieved when compared with that of DXMA-sol. DXMA-NLCs exhibited a significant anti-inflammatory and hepatoprotective effect on carrageenan-induced rats and carbon tetrachloride-induced mice compared with DXMA-sol. However, the effect was not in proportion to the dosage. The intermediate and low dosages presented better effects than DXMA-sol. All results indicate that NLCs, as a novel carrier for DXMA, has potential for the treatment of liver diseases, increasing the cure efficiency and decreasing the side effects on other tissues.