Mitoxantrone Loaded Superparamagnetic Nanoparticles for Drug Targeting: A Versatile and Sensitive Method for Quantification of Drug Enrichment in Rabbit Tissues Using HPLC-UV

Abstract

In medicine, superparamagnetic nanoparticles bound to chemotherapeutics are currently investigated for their feasibility in local tumor therapy. After intraarterial application, these particles can be accumulated in the targeted area by an external magnetic field to increase the drug concentration in the region of interest (Magnetic-Drug-Targeting). We here present an analytical method (HPLC-UV), to detect pure or ferrofluid-bound mitoxantrone in a complex matrix even in trace amounts in order to perform biodistribution studies. Mitoxantrone could be extracted in high yields from different tissues. Recovery of mitoxantrone in liver tissue (5000 ng/g) was 76 ± 2%. The limit of quantification of mitoxantrone standard was 10 ng/mL ±12%. Validation criteria such as linearity, precision, and stability were evaluated in ranges achieving the FDA requirements. As shown for pilot samples, biodistribution studies can easily be performed after application of pure or ferrofluid-bound mitoxantrone.

Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

“…Depending on the amount of MTO bound to the particles, SPION had a hydrodynamic diameter of approximately 100 nm, as determined by dynamic light scattering. Under defined conditions of SPION content, dilution, and flow rate, quantifying MTO bound to SPION in this way can compete with the established HPLC method used to determine loading efficiency [16]. …”

“…To analyze the MTO-content of the ferrofluid, MTO was extracted from 100 μL ferrofluid by the addition of 900 μL 1N HCl and incubation in a Thermomixer ® comfort (Eppendorf AG, Hamburg, Germany) at 600 rpm and room temperature for 1 h. After centrifuging with a Minispin ® plus (Eppendorf AG, Hamburg, Germany) at 14,500 rpm for 10 min, the supernatant was measured with HPLC, using a Waters Alliance model consisting of a separation module (2695 series), a dual wavelength absorbance detector (2487 series), and a 3.0 × 100 mm X-Bridge phenyl column (Waters, Germany). The mobile phase consisted of formiate buffer (pH 3.0) and methanol (80:20 v / v ) [16]. …”

Cancer therapy with drug loaded magnetic nanoparticles—magnetic drug targeting

“…We established an efficient protocol concerning selective HPLC measuring of MTO after nanoparticle application (Fig. 2) and this was described previously [5]. Many accompanying experiments are necessary to enlighten the physical and physiological functionality of MDT.…”

Magnetic microgels for drug targeting applications: Physical–chemical properties and cytotoxicity evaluation

“…UV-B sterilized microgels were incubated with mitoxantrone (MTO) for 96 h. The effective loading of nanoparticles with MTO was calculated from the measurements of unbound MTO in the supernatant by an established HPLC method [18].…”