Screening of Lipid Carriers and Characterization of Drug-Polymer-Lipid Interactions for the Rational Design of Polymer-Lipid Hybrid

Purpose. The thermodynamics and solid state properties of components and their interactions in a formulation for polymer-lipid hybrid nanoparticles (PLN) were characterized for screening lead lipid carriers and rational design of PLN. Methods. Verapamil HCl (VRP) was chosen as a model drug and dextran sulfate sodium (DS) as a counter-ionic polymer. Solubility parameters of VRP, VRP-DS complex, and various lipids were calculated and partition of VRP and VRP-DS in lipids was determined. Thermodynamics of VRP binding to DS was determined by isothermal titration calorimetry (ITC). The solid state properties of individual components and their interactions were characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Results. Dodecanoic acid (DA) was identified as the best lipid carrier among all lipids tested based on the solubility parameters and partition coefficients. VRP-DS complexation was a thermodynamically favorable process. Maximum binding capacity of DS and the highest drug loading capacity of DA were obtained at an equal ionic molar ratio of DS to VRP. In the PLN formulation, DA remained its crystal structure but had a slightly lower melting point, while VRP-DS complex was in an amorphous form. Conclusions. Drug loading efficiency and capacity of a lipid matrix depend on the VRP-DS binding and the interactions of the complex with the lipid. A combined analysis of solubility parameters and partition coefficients is useful for screening lipid candidates for PLN preparation. KEY WORDS: drug-polymer complex; isothermal titration calorimetry; partition coefficient; polymer-lipid hybrid nanoparticles (PLN); solid lipid nanoparticles; solubility parameters