Document Type: Research article
Biomedical Engineering Division, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Innovation Center for Advanced Technology, Matrix, Inc., New York 10029, USA.
Cationic polymeric nanoparticles have great potential for developing drug delivery systems
with limited side effects for tumor medication. The goal of this research is investigation of
cationic dextran-spermine polymer (DS) efficacy for improvement of hydrophilic drug delivery
to negatively charged cancerous cells. Capecitabine (as a hydrophilic antineoplastic drug) was
loaded into the magnetic dextran-spermine nanoparticles (DS-NPs) via ionic gelation. Design
of experiments was applied to specify how the significant factors affect size, surface charge and
capecitabine entrapment efficiency of the DS-NPs. Physicochemical properties, in-vitro release
profile and cellular studies of the optimized DS-NPs were evaluated. The experimental results
indicated that DS-NPs with favorable properties can be achieved at an optimized condition of
2 mg/mL DS and 0.75 mg/mL tri-polyphosphate (TPP) concentrations, TPP addition rate of 35
mL/min, pH 3 of DS solution and super paramagnetic iron oxide nanoparticles (SPION)/DS
mass ratio of 0.5. The entrapment efficiency of capecitabine was 26.1% at optimum condition
and drug release at neutral pH after 24 h and acidic pH within 3 h was 56 and 98%, respectively.
The cytotoxicity assessment exhibited that capecitabine loaded DS-NPs was more toxic than
corresponding free drug as control. Significant cellular uptake of capecitabine loaded DS-NPs
by U87MG glioblastoma cells were proved by Prussian blue staining and TEM, qualitatively.
DS-NPs are suitable candidates for delivery of the hydrophilic drugs in cancer treatment and
due to positive charge of the dextran-spermine, the uptake of the hydrophilic drugs by the
cancerous cells was improved.