In-Vitro Assessment of Magnetic Dextran-Spermine Nanoparticles for Capecitabine Delivery to Cancerous Cells

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.