A method for the prediction of drug content of poly(lactic-co-glycolic)acid drug carrier nanoparticles obtained by nanoprecipitation

摘要

Poly(lactic-co-glycolic acid) drug loaded nanoparticles are applied successfully to increase the distribution and bioavailability of hydrophobic drug molecules, although the generally low drug content implies a limitation. Poly(lactic-co-glycolic acid) nanoparticles were prepared by nanoprecipitation to encapsulate model drugs, a series of alkyl-hydroxy-benzoate (parabens) from methyl-to octyl with increasing hydrophobicity to address the influence of drug property on the encapsulation. The drug content and encapsulation efficiency were found to be substantially different for the various parabens. The analysis of the miscibility of the polymer with parabens using their solubility parameters could not provide satisfactory explanation for the experimental findings.The treatment of nanoencapsulation however, as a partitioning process involving poly(lactic-co-glycolic acid) and aqueous phase led to a relationship between the drug content of the nanoparticles and the characteristic properties of the drug molecule. According to that both the high hydrophobicity and high aqueous solubility of the drug favour the efficacy of its encapsulation. The actual and also the achievable maximum drug content can be predicted and was tested in several systems. The above approach opens the way for more reasonable design of nanoparticle drug carrier in addition to the possible explanation for the drug content achievable for a given compound.