Delivery Of Anticancer Drug Doxorubicin Research Articles

Halloysite Nanotubes, a Multifunctional Nanovehicle for Anticancer Drug Delivery

AbstractTargeted drug delivery systems have attracted a great deal of interest by virtue of their potential use in chemotherapy. In this study, multicomponent halloysite nanotubes (HNTs) have been evaluated as a platform to assist and direct the delivery of anticancer drug doxorubicin (DOX) into cancer cells. Folic acid (FA) and magnetite nanoparticles were successfully grafted onto HNTs via amide reaction whereas the drug has been introduced by capitalizing electrostatic interaction between cationic drug and anionic exterior of HNTs, which eventually leads to pH responsive release. The resultant DOX loaded FA‐Fe3O4@HNTs were well characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and XRD. The clinical efficacy of the system was validated by confocal microscopy and cell cytotoxicity assay (MTT assay). MTT assay results revealed a high biocompatibility up to a concentration of 200 µg/mL of HNTs, while, DOX loaded FA‐Fe3O4@HNTs were markedly cytotoxic to HeLa cells. This multifunctional nanovehicle has a great potential for cancer diagnosis and therapy, and could further advance the clinical use of nanomedicine.

Design of pH-responsive nanoparticles of terpolymer of poly(methacrylic acid), polysorbate 80 and starch for delivery of doxorubicin

This work focused on the design of new pH-responsive nanoparticles for controlled delivery of anticancer drug doxorubicin (Dox). Nanoparticles of poly(methacrylic acid)-polysorbate 80-grafted starch (PMAA-PS 80-g-St) were synthesized by using a one-pot method that enabled simultaneous grafting of PMAA and PS 80 onto starch and nanoparticle formation in an aqueous medium. The particles were characterized by FTIR, 1H NMR, TEM, DLS, and potentiometric titration. Dox loading and in vitro release from the nanoparticles were investigated. The FTIR and 1H NMR confirmed the chemical composition of the graft terpolymer. The nanoparticles were relatively spherical with narrow size distribution and porous morphology. They exhibited pH-dependent swelling in a physiological pH range. The particle size and magnitude of phase transition were dependent on polymer composition and formulation parameters such as concentrations of surfactant and cross-linking agent and total monomer concentration. The nanoparticles with optimized compositions showed high loading capacity for Dox and sustained Dox release. The results suggest that the new pH-responsive terpolymer nanoparticles are useful in controlled drug delivery.

A Novel Cancer Targeting Approach Based on Estrone Anchored Stealth Liposome for Site-Specific Breast Cancer Therapy

We here report the successful utilization of estrogen receptor (ER) for the delivery of anticancer drug doxorubicin (DOX) encapsulated within pegylated liposome for the treatment of breast cancer. Estrone (ES) was anchored as ligand on to stealth liposome (ES-SL-DOX) for targeting to ERs. In vitro cytotoxicity study was conducted on ER positive and negative breast carcinoma cells. The fluorescent microscopy studies were performed with estrone anchored stealth liposome (ES-SL) loaded with 6-carboxyfluorescein (6-CF). Pharmacokinetic, tissue distribution studies and tumor growth inhibition were carried out followed by intravenous (i.v.) administration of liposomal formulations. ES-SL-DOX demonstrated strongest cytotoxicity to the ER positive cell lines as compared to non-targeted formulations i.e. SL-DOX and plain DOX confirming that ES-SL-DOX was effectively taken up by cells expressing ERs. The half-life (t(1/2)) of SL-DOX and ES-SL-DOX was about 9 and 13 fold higher than that of the free DOX, respectively. Accumulation of ES-SL-DOX in the tumor tissue was 24.27 and 6.04 times higher as compared to free DOX and SL-DOX respectively, after 8 h. ES-SL-DOX at a dose of 5 mg DOX/kg resulted in effective retardation of tumor growth. These findings support that estrogen receptor(s) may be utilized as potential target for chemotherapy of cancers and estrone anchored stealth liposomes could be one of the promising solutions for the delivery of anticancer agent to breast tumors with reduced side-effects.

Preparation of folate-conjugated starch nanoparticles and its application to tumor-targeted drug delivery vector

Anion starch nanoparticles (StNP) were prepared in water-in-oil microemulsion. Folate modified with PEG was conjugated to the surface of StNP to obtain the folate-conjugated starch nanoparticles (FA-PEG/StNP). The average diameter of FA-PEG/StNP determined by AFM and Zeta-Sizer apparatus was about 130 nm. Doxorubicin (DOX)-loaded FA-PEG/StNP was obtained via infiltrating combination. The result of UV spectrophotometer showed that the saturation concentration of DOX-loaded FA-PEG/StNP was 28 μg/mg, which was effective for the controlled release of anticancer drug DOX. The cell experiments showed that the Lc50 of DOX-loaded FA-PEG/StNP and DOX-loaded StNP was higher than that of DOX, which indicates that FA-PEG/StNP and StNP can decrease the toxicity of DOX; while the lethal rate of DOX-loaded FA-PEG/StNP was 3 times that of DOX-loaded StNP with the same quantity of DOX, which indicates that FA in FA-PEG/StNP is effective for improving the targeting function of nanoparticles, thus enhancing the inhibition effect of anticancer drug to cancer cell. This work demonstrates that the FA-PEG/StNP system is a potentially useful system for the targeted delivery of anticancer drug DOX.