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Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy.

ABSTRACT: Superparamagnetic iron oxide nanoparticles (SPIONs) and oxaliplatin (OHP) were in-situ encapsulated in pectin cross-linked with Ca(2+) forming 100-200 nm sized magnetically functionalized pectin nanocarriers, referred here as MP-OHP nanocarriers. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed formation of spherical nanostructures. The magnetic measurements by vibration sample magnetometer (VSM) revealed high saturation magnetization (M s=45.65 emu/g). The superparamagnetic property of MP-OHP was confirmed from the blocking temperature (T B) determined from field cooled and zero field cooled magnetization, measured by superconducting quantum unit interference device (SQUID) magnetometry. The stability of the aqueous dispersion of MP-OHP nanocarriers was confirmed from its high zeta potential (-30.5 mV). The drug encapsulation efficiency (55.2±4.8% w/w) and the drug loading content (0.10±0.04 wt%) in MP-OHP nanocarriers were determined from corresponding platinum contents in OHP and MP-OHP batches measured by inductively coupled plasma mass spectrometry (ICPMS). These nanocarriers exhibited a sustained release of OHP in phosphate buffer solution maintained at pH 5.5 and 7.4, where the drug release profile satisfied a combination of diffusion and swelling controlled mechanism. The cytotoxicity effect of MP-OHP nanocarriers was studied on MIA-PaCa-2 (pancreas) cancer cell line, where the GI50 values were more than 5 mg/mL and it exhibited 10 folds higher cytoxicity than the equivalent concentration of free drug.

SUBMITTER: Dutta RK

PROVIDER: S-EPMC4210274 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy.

Dutta Raj Kumar RK Sahu Saurabh S

Results in pharma sciences 20120522

Superparamagnetic iron oxide nanoparticles (SPIONs) and oxaliplatin (OHP) were in-situ encapsulated in pectin cross-linked with Ca(2+) forming 100-200 nm sized magnetically functionalized pectin nanocarriers, referred here as MP-OHP nanocarriers. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed formation of spherical nanostructures. The magnetic measurements by vibration sample magnetometer (VSM) revealed high saturation magnetization (M s=45.65 ...[more]

PMID: 25755993

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Project description:BackgroundImproving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs.Materials and methodsHerein, we designed a novel DDS based on magnetic mesoporous silica core-shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors.ResultsNanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects.ConclusionThese results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy.

Dataset Information

Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy.

Publications

Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy.

Similar Datasets

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