Jinming Zhang,Yingbo Li,Wei Gao,Michael A Repka,Yitao Wang,Meiwan Chen
Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo.Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat.Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 – ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension.Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
Liu Xiaoning,Xu Yuling,Kang Jingjing,Wang Hui,Huang Tao
Mesoporous Silica Nanoparticles (MSNs) loaded with lycorine were previously reported to induce apoptosis of prostate cancer cells with remarkably enhanced efficiency and reduced side effects. In the current study, MSNs-based co-delivery of lycorine and/or the tumor suppressor gene p53
was developed for drug delivery to chronic myelocytic leukemia (CML) cell line K562. We have demonstrated that the simultaneous delivery of lycorine and p53 via MSNs achieved synergistic anti-proliferative and pro-apoptotic effects on K562 cells when compared to MSNs loaded with lycorine only.
The cell viability assay on K562 cells showed that the half-maximal inhibitory concentration (IC50) after 48 h of treatment with MSNs@Lycorine@pcDNA3.1-p53 was only 20% of that for MSNs@Lycorine. Furthermore, the Annexin V-FITC/PI assay for K562 cell apoptosis demonstrated a markedly
higher apoptotic rate in the group treated with MSNs@Lycorine@pcDNA3.1-p53 when compared to that of the MSNs@Lycorine group; this result was consistent with the accumulation of the p53 protein. These findings indicate that MSNs could be an ideal nanovector for simultaneous delivery of drugs
and genes for improved cancer therapy and that an MSN-based lycorine/wt-p53 co-delivery system with efficient endocytosis, sustained drug-releasing property, excellent biocompatibility, and enhanced synergistic proapoptotic effects might be a new promising strategy for the treatment of CML.
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