|
|
|
|
|
|
Browse Articles |
|
|
|
|
|
Journal Links |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sci. Lett. J. 2015, 4: 125
|
|
|
|
Research Article
|
|
|
|
|
|
|
Full Text
|
|
|
|
RGD-modified anticancer drug containing hybrid nanoparticles for the treatment of integrins overexpressing glioma cells
|
|
|
|
Udita Agrawala, Gousia Chashoob, Parduman Raj Sharmab, Ashok Kumarb, Ajit kumar Saxenab, S. P. Vyasa
|
|
|
|
|
|
|
|
a Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, M.P., India, 470003
b Cancer Pharmacology Division, Indian Institute of Integrative Medicine, Jammu, India, 180001
|
|
|
|
|
|
|
|
Abstract |
|
|
|
Glioma therapy needs a specially designed nanocarrier that is proficient to overcome the blood–brain barrier and blood-tumor barrier and selectively taken up by glioma cells. cRGDfK functionalized polymer lipid hybrid nanoparticles (NPs) were prepared and characterized for docetaxel (DTX) targeting potential against integrin rich brain tumors. Glioma cells overexpress avß3 integrin receptors that can specifically recognize and internalize cRGDfK decorated nanocarrier system. NPs demonstrated high encapsulation efficiency with pH-dependent release profile. DTX-loaded cRGDfK modified NPs (DNPs-RGD) significantly inhibit cellular proliferation (lowest IC50) in U87 glioma cells when compared with free DTX and non-targeted NPs. The DNPs-RGD can be efficiently transported across the in-vitro BBB model and target glioma cells. The cell uptake results indicate that cRGDfK modification enhances the delivery of chemotheraptics exclusively inside the cell via integrin receptor-mediated endocytosis. Moreover, DNPs-RGD reduced the tumor volume significantly as demonstrated by in vivo anti-tumor activity in glioma bearing rats. The median survival time for brain tumor bearing rats treated with DNPs-RGD (38 days) was extended very significantly as compared to DNPs (28 days) and DTX (15 days). From the results it can be concluded that cRGDfK targeted NPs has the potential to be used as an effective nanocarrier system to conquer the hurdles in drug delivery to the brain, providing a novel approach to glioblastoma therapy.
|
|
|
|
|
|
|
|
Keywords
|
|
|
|
Glioma; Docetaxel; U87; Cancer therapy; Polymer lipid hybrid nanoparticle; cRGDfK
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|