ABSTRACT
OBJECTIVE: To construct a novel daunorubicin-loaded microparticles (DNR-MPs) drug delivery system, and study its proliferation inhibiton effect on leukemia cells. METHODS: Both DNR-MPs-IDL(DNR microparticles with intracellular drug loading method) and DNR-MPs-EDL (DNR microparticles with extracellular drug loading method) were prepared from HL-60 cells, and the average particle size, Zeta potential and drug loading efficiency of DNR-MPs were measured. The uptake of DNR-MPs by HL-60 cells was analyzed by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). The inhibition effect of DNR-MPs on the proliferation of HL-60 cells was evaluated by MTT assay. RESULTS: There was no significant difference in the average particle size and Zeta potential of the two DNR-MPs. The drug loading efficiency of DNR-MPs-EDL was higher compared with DNR-MPs-IDL. The uptake results showed that the two DNR-MPs significantly increased the drug uptake compared with free DNR (P < 0.05). DNR-MPs- IDL showed a higher drug uptake by the cells than DNR-MPs-EDL did (P < 0.05). They also exhibited an enhanced inhibition effect on the proliferation of HL-60 cells compared with DNR (P < 0.05). CONCLUSION: The different ways of preparation of drug-loaded microparticles can cause varying anti-tumor effect. Microparticles can significantly augment the anti-leukemia efficacy of DNR, indicating a promising drug carrier for the therapy of leukemia.
ABSTRACT
In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone ⅡA loaded immunoliposome (CD123-TanⅡA-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the TanⅡA-loaded PEGylated liposomes (TanⅡA-LP) of S100PC-Chol-(mPEG2000-DSPE)-TanⅡA at 19∶5∶1∶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-TanⅡA-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE. The cellular uptake assay was measured by flow cytometry, and the inhibitory effect of CD123-TanⅡA-ILP on NB4 cells proliferation was tested by using MTT assay. The results of cellular uptake assay showed that CD123-ILP could significantly increase the drug uptake of NB4 cells as compared with free drugs and LP. The IC₅₀ values at 48 h incubation were 20.87, 11.71, 7.17 μmol•L⁻¹ respectively for TanⅡA，TanⅡA-LP and CD123-TanⅡA-ILP. CD123-ILP demonstrated a potential and promising targeted drug delivery strategy for acute myelogenous leukemia (AML) treatment.