Compound Stability in Nanoparticles: The Effect of Solid Phase Fraction on Diffusion of Degradation Agents into Nanostructured Lipid Carriers.

Abstract

The stability of active compounds encapsulated in nanoparticles depends on the resistance of the particles to diffusion of environmental degradation agents. In this paper, off-lattice Monte Carlo simulations are used to investigate a suspension of nanostructured lipid carriers (NLC) composed of interspaced liquid and solid lipid domains, immersed in a solution containing molecules representing oxidative or other degradation agents. The simulations examine the diffusion of the degradation agents into the nanoparticles as a function of nanoparticle size, solid domain fraction, and domain size. Two types of suspensions are studied: one (representing an infinitely dilute nanoparticle suspension) where the concentration of oxidative agents is constant in the solution around the particle and the other, finite system where diffusion into the nanoparticle causes depletion in the concentration of degradation agents in the surrounding solution. The total number of degradation agent molecules in the NLCs is found to decrease with the solid domain fraction, as may be expected. However, their concentration in the liquid domains is found to increase with the solid domain fraction. Since the degradation reaction depends on the concentration of the degradation agents, this suggests that compounds encapsulated in nanoparticles with high liquid content (such as emulsions) will degrade less and be more stable than those encapsulated in NLCs with high solid domain fraction, in agreement with previous experimental results.