Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential

Abstract

Drug carrier systems based on lipid nanosuspensions prepared by melt emulsification present a number of severe stability problems such as a high gelation tendency, considerable particle growth and drug expulsion. Destabilization of the emulsified lipidic carriers is related to recrystallization of the lipids. The choice of stabilizers for colloidal lipid suspensions is, therefore, restricted. Systematic surface modifications are thus limited. In addition, the drug payload of crystalline nanosuspension particles is generally low. Improved stability and loading capacities were found for amorphous lipid nanoparticles which present the characteristic signals of supercooled melts in high resolution 1H-NMR. The NMR data indicate that such liquid but viscous carriers can, however, not immobilize the incorporated drug molecules to the same extent as a solid matrix. Sustained release over days or weeks as in slowly biodegraded solid matrices thus seems difficult to achieve with a supercooled melt. Attempts to combine the advantages of the solid crystalline lipids and the amorphous nature of the supercooled melts by generating solid but amorphous lipid suspension particles with a satisfactory long-term stability by a variation of the lipid matrix material have hitherto not been successful. Even a satisfactory stabilization of the α-modification using complex lipid mixtures to improve the loading capacity or to slow down the drug expulsion process could not be achieved. The rates of the polymorphic transitions were much higher in the colloidal lipid dispersions than in the bulk for the hard fats under investigation. Despite the fact that the properties of the lipids are superimposed with colloidal properties, significant differences between monoacid triglycerides and complex lipids were, however, found.