Browsing by Author "Mu, Qingxin"

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Hexanoyl-Chitosan-PEG Copolymer Coated Iron Oxide Nanoparticles for Hydrophobic Drug Delivery
(2015-04-01)
Hsiao, Meng-Hsuan
;
Mu, Qingxin
;
Stephen, Zachary R.
;
Fang, Chen
;
Zhang, Miqin
Nanoparticle (NP) formulations may be used to improve in vivo efficacy of hydrophobic drugs by circumventing solubility issues and providing targeted delivery. In this study, we developed a hexanoyl-chitosan-PEG (CP6C) copolymer coated, paclitaxel (PTX)-loaded, and chlorotoxin (CTX) conjugated iron oxide NP (CTX-PTX-NP) for targeted delivery of PTX to human glioblastoma (GBM) cells. We modified chitosan with polyethylene glycol (PEG) and hexanoyl groups to obtain the amphiphilic CP6C. The resultant copolymer was then coated onto oleic acid-stabilized iron oxide NPs (OA-IONP) via hydrophobic interactions. PTX, a model hydrophobic drug, was loaded into the hydrophobic region of IONPs. CTX-PTX-NP showed high drug loading efficiency (>30%), slow drug release in PBS and the CTX-conjugated NP was shown to successfully target GBM cells. Importantly, the NPs showed great therapeutic efficacy when evaluated in GBM cell line U-118 MG. Our results indicate that this nanoparticle platform could be used for loading and targeted delivery of hydrophobic drugs.
Stable and Efficient Paclitaxel Nanoparticles for Targeted Glioblastoma Therapy
(2015-06-03)
Mu, Qingxin
;
Jeon, Mike
;
Hsiao, Meng-Hsuan
;
Patton, Victoria K.
;
Wang, Kui
Development of efficient nanoparticles (NPs) for cancer therapy remains a challenge. NPs are required to have high stability, uniform size, sufficient drug loading, targeting capability, and ability to overcome drug resistance. In this study, the development of a NP formulation that can meet all these challenging requirements for targeted glioblastoma multiform (GBM) therapy is reported. This multifunctional NP is composed of a polyethylene glycol-coated magnetic iron oxide NP conjugated with cyclodextrin and chlorotoxin (CTX) and loaded with fluorescein and paclitaxel (PTX) (IONP-PTX-CTX-FL). The physicochemical properties of the IONP-PTX-CTX-FL are characterized by transmission electron microscope, dynamic light scattering, and high-performance liquid chromatography. The cellular uptake of NPs is studied using flow cytometry and confocal microscopy. Cell viability and apoptosis are assessed with the Alamar Blue viability assay and flow cytometry, respectively. The IONP-PTX-CTX-FL had a uniform size of approximate to 44 nm and high stability in cell culture medium. Importantly, the presence of CTX on NPs enhanced the uptake of the NPs by GBM cells and improved the efficacy of PTX in killing both GBM and GBM drug-resistant cells. The IONP-PTX-CTX-FL demonstrated its great potential for brain cancer therapy and may also be used to deliver PTX to treat other cancers.