Abstract
Levamisole (LEVA) is used to treat worm infections, but it can also inhibit cancer cell growth by inhibiting the aldehyde dehydrogenase pathway. Therefore, here, we developed a drug carrier targeting CD133, a biomarker overexpressed in ovarian cancer cells. The particle structure and cytotoxicity of the prepared LEVA-containing particles—called LEVA/PVP/PMMA microparticles (MPs) (because it used matrix material polyvinylpyrrolidone (PVP) and poly(methylmethacrylate) (PMMA))—were investigated in the ovarian cancer cell lines SKOV-3 and CP70. The particle size of the MPs was determined to be 1.0–1.5 µm and to be monodispersed. The hydrophilic property of PVP created a porous MP surface after the MPs were soaked in water for 20 min, which aided the leaching of the hydrophilic LEVA out of the MPs. The encapsulation efficiency of LEVA/PVP/PMMA MPs could reach up to 20%. Free-form LEVA released 50% of drugs in <1 h and 90% of drugs in 1 day, whereas the drug release rate of LEVA/PVP/PMMA MPs was much slower; 50% released in 4 h and only 70% of drugs released in 1 day. In the in vitro cell model test, 5 mM free-form LEVA and 0.1 g/mL CD133 targeted LEVA/PVP/PMMA MPs reduced SKOV-3 cell viability by 60%; 0.1 g/mL LEVA/PVP/PMMA MPs was equivalent to a similar dosage of the free drug. In addition, the cytotoxicity of CD133-conjugated LEVA/PVP/PMMA MPs shows a different cytotoxicity response toward cell lines. For SKOV-3 cells, treatment with free-form LEVA or CD133-conjugated LEVA/PVP/PMMA MPs exerted dose-dependent cytotoxic effects on SKOV-3 cell viability. However, CD133-conjugated LEVA/PVP/PMMA MPs demonstrated no significant dose-dependent cytotoxic efficacy toward CP70 cells.
Highlights
Ovarian cancer is the leading cause of death in women because of its high recurrence rate and eventual resistance to cytotoxic chemotherapy [1,2]
Some researchers reported the use of microparticles for using in drug delivery [8,9], like encapsulation of enzymes for gastrointestinal delivery, implantation for sustained release and for embolization chemotherapy
LEVA/PVP/PMMA MP morphology was observed in scanning electron microscopy (SEM) images
Summary
Ovarian cancer is the leading cause of death in women because of its high recurrence rate and eventual resistance to cytotoxic chemotherapy [1,2]. Several nanoparticles (NPs) have been extensively developed to overcome drug resistance. The NP-based drug delivery system is highly effective in cancer treatment because of its specific penetration ability, intracellular delivery, and feature of interacting with a high surface area of cells. NPs increase the concentration of therapeutic payloads at the disease site, which minimizes the side effects of the therapeutic drug [3,4,5,6,7]. Some researchers reported the use of microparticles for using in drug delivery [8,9], like encapsulation of enzymes for gastrointestinal delivery, implantation for sustained release and for embolization chemotherapy
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