Development and Optimization of ivermectin-lipid nanocapsules intend for oral administration

ULLIO GAMBOA G; LLOLO G; BENOIT J; PALMA S. D; ALLEMANDI D,

Córdoba

Congreso; Tercera Reunión Internacional de Ciencias Farmacéuticas - RICIFA 2014; 2014

Facultad de Ciencias Quimicas - UNC

Introduction P-glycoprotein (P-gp), an ATP-dependent drug efflux pump, plays a major role in the transport of various drugs. Lipid nanocapsules (LNC) emerged as promissory alternative as drug delivery system.The main advantages of LNC lie in their ability i) to increase the solubility of hydrophobic compounds, (ii) to increase intracellular internalization, (iii) to improve in vitro and in vivo stability. IVM is a broad-spectrum antihelmintic agent reported as a P-gp substrate. Taking into account these, the goal of this work has been to develop LNC suitable for the encapsulation of IVM. Materials & Methods The LNC were prepared by the phase inversion process and optimized using a DoE approach to obtain nanoparticules within the size range of 50 nm. This related domain was named the ?feasibility domain?. Once the feasibility zone was identified, IVM was loaded into the LNC. Size, polydispersity and zeta potential were analyzed by photon correlation spectroscopy. IVM encapsulation efficiency was determined by HPLC technique. CaCo-2 cell viability was estimated by the MTS assay and the stability in simulated gastrointestinal media was also evaluated. Results & Discussion Following the optimization process, both blank and IVM-loaded LNC formed monodispersed populations with a mean size around 50 nm and a slightly negative charge surface. Due to its hydrophobic character, IVM was efficiently encapsulated into the optimized LNC with an encapsulation efficiency of about 90%. The cytotoxicity studies indicated that both formulations were not toxic in the evaluated concentrations. Finally, the stability in gastric and intestinal media confirmed that this formulation could be suitable for oral administration. Conclusions We report evidence about the feasibility of a lipid-core nanoformulation optimized for IVM encapsulation. The high entrapment of IVM in LNCs supplies a new pharmacological tool to treat endo and ecto parasites. Additional studies are underway to determine the potential therapeutic activity of IVM-LNC after an oral delivery in rats.