Abstract:
Dual-targeting nanostructure lipid carriers loading mitoxantrone hydrochloride(ALN-FOL-MTO-NLCs)were prepared by solvent evaporation. ALN-FOL-MTO-NLCs was quasi-spherical shapes observed by AFM and the mean particle size, Zeta potential and entrapment efficiency were(45. 9±2. 7)nm, -(16. 78±2. 17)mV and(99. 7±0. 1)%, respectively. In
in vitro studies, ALN-FOL-MTO-NLCs showed good binding ability to hydroxyapatite, a model component of bone minerals, whereas unmodified NLCs yielded only nonspecific binding. The cellular uptake efficiency of ALN-FOL-NLCs were 3. 19 times more than that of unmodified NLCs. The pharmacokinetics in rats and biodistribution in mice of NLCs loading MTO after intravenous injection were investigated by HPLC. The AUC of the blood PK profile of the drug formulated in ALN-FOL-MTO-NLCs were 5. 0 and 63. 1 times that of unmodified NLCs and free drug(MTO-INJ), respectively. The AUC of the bone PK profile of the drug formulated in ALN-FOL-MTO-NLCs was 3. 7-fold and 5. 0-fold higher than that of FOL-MTO-NLCs and MTO-INJ, respectively. Compared with FOL-MTO-NLCs, ALN-FOL-MTO-NLCs displayed a reduction in drug toxicity because of the reduced accumulation in liver, spleen, heart and kidney. In turn, this allows administration of larger and more efficacious drug doses. In conclusion, compared with MTO-INJ and MTO-NLCs, ALN-FOL-MTO-NLCs displayed longer circulating capability, better bone targeting ability and tumor cells targeting efficiency.