A Rapid and Sensitive HPLC Method for Simultaneous Determination of Irinotecan Hydrochloride and Curcumin in Co-delivered Polymeric Nanoparticles

In recent years, a great deal of attention has been paid to the combined use of multiple antitumor drugs for better cancer treatment. The aims of the study are to construct a nanoparticle drug delivery system for the co-delivery of irinotecan hydrochloride and curcumin and to develop an analytical method for simultaneously quantifying these molecules, which is essential for further studies of the co-delivered nano system. The irinotecan hydrochloride and curcumin co-delivered nanoparticle (ICN) were prepared by combinatorially entrapping them into polyethylene glycol–poly lactic acid-co-glycolic acid (PEG–PLGA) polymeric nanoparticles. A simple, sensitive and rapid high-performance liquid chromatography method was developed and validated to simultaneously quantify the compounds in the co-delivered nanoparticle system. Acetonitrile and ultrapure water containing sodium dodecyl sulfate (0.08 mol/L), disodium phosphate (Na2HPO4, 0.002 mol/L) and acetic acid (4%, v/v) were used as the mobile phase and their ratio was set at 50:50. The flow rate was set to 1.0 mL/min, and the temperature in the column oven was maintained at 40°C. The analysis was carried out at 256 and 424 nm to assess irinotecan hydrochloride and curcumin, respectively. Detectors with only one channel can also visualize both analytes in one chromatogram at 379 nm and still demonstrate acceptable sensitivity. The retention times for irinotecan hydrochloride and curium were 3.317 and 5.560 min, respectively. The method developed was confirmed to be sensitive, accurate (recovery, 100 ± 2%), precise (relative standard deviation, RSD ≤ 1%), robust and linear (R2 ≥ 0.9996) in the range from 2.05 to 1050 μg/mL. The presented method has been used to quantify irinotecan hydrochloride and curcumin in the co-delivered ICN nano system to assess the drug delivery quality of the nanoparticles and can also be used for routine analysis because of its simplicity and accuracy.

Molecular Docking Studies and Inhibition Properties of Some Antineoplastic Agents against Paraoxonase-I

Background: Currently, most of the drugs used in clinical applications show their pharmacological influences by inhibiting or activating enzymes. Therefore, enzyme inhibitors have an essential place in the drug design for many diseases. Objective: The current study aimed to contribute to this growing drug design field (i.e., medicine discovery and development) by analyzing enzyme-drug interactions. Methods: For this reason, Paraoxonase-I (PON1) enzyme was purified from fresh human serum by using rapid chromatographic techniques. Additionally, the inhibition effects of some antineoplastic agents were researched on the PON1. Results: The enzyme was obtained with a specific activity of 2603.57 EU/mg protein. IC50 values for pemetrexed disodium, irinotecan hydrochloride, dacarbazine, and azacitidine were determined to be 9.63μM, 30.13μM, 53.31μM, and 21.00mM, respectively. These agents found to strongly inhibit PON1, with Ki constants ranging from 8.29±1.47μM to 23.34±2.71mM. Dacarbazine and azacitidine showed non-competitive inhibition, while other drugs showed competitive inhibition. Furthermore, molecular docking was performed using maestro for these agents. Among these, irinotecan hydrochloride and pemetrexed disodium possess the binding energy of -5.46 and -8.43 kcal/mol, respectively. Conclusion: The interaction studies indicated that these agents with the PON1 possess binding affinity.