Background: Successful nanoparticles formulations include Abraxane® (an albumin bound nanoparticle paclitaxel), Genexol-PM® (a polymer bound nanoparticle paclitaxel), and Doxil®. At LipoMedics we have developed a unique nanomedicinization process of water insoluble drug for intravenous administration using combination of solvents and polymers. The polymers can be simple phospholipid or synthetic diblock polymer or complex protein such as albumin. Electrochemistry was used to understand the molecular organization of these nanoparticles and biosensor built to support the in process monitoring of this pharmaceutic.

Materials and Methods: Nanoparticle synthesis was conducted using a two step method whereby the drug is first emulsified in presence of solvent and then nanofabricated in presence of polymer. Nanoparticle size and zeta potential were measured using a Malvern ZS DLS system. The formulation was subjected to serial filtration using 1.2µm, 0.8µm, 0.45µm and 0.2µm syringe filters. The drug incorporation/loading was measured using ELISA. Electrochemical properties of the formulation were measured using screen printed carbon nanotube (CNT) electrodes from DropSens and a PGSTAT204 Autolab Potentiostat from Metrohm. The drug being evaluated in this study is paclitaxel- a water insoluble drug that can only be solubilized in Cremophor EL for intravenous administration. Only nanomedicinization allowed paclitaxel to be formulated without solvent.

Results:A series of stable nanomedicinized paclitaxel formulations were created using chloroform or ethanol as solvent and phospholipid or albumin as polymer. Each formulation exhibited a distinct cyclic voltammetry (CV) scan. The CV scan was highly dependent on the polymer used. Monolayer and bilayer phospholipids behaved similarly as polymer with or without paclitaxel. Increasing the loading of these phospholipid nanoparticles caused a shift from profiles of high capacitance material to profiles of low capacitance material.

Discussion: Capacitance of a carbon-based electrode consists of two major components: the electrical double layer capacitance due to the electrostatic attraction of charged carbon surfaces to electrolyte ions and the pseudocapacitance due to the Faradic reactions of electroactive species on the carbon surfaces. During electrochemical evaluations, the nanoparticles were treated as ionic liquid capacitance material. Low capacitance is suggestive of weakened charge accumulation in the electrode - electrolyte interface which depends on the mesoporosity and electrolyte accessibility of the capacitive material.