Encapsulation of Hydrophilic and Lipophilic Drugs in PLGA Nanoparticles by the Nanoprecipitation Method

Abstract

The purpose of this study was to assess the relative advantages and drawbacks of the nanoprecipitation-solvent displacement method for a range of drugs with respect to the particle size and drug encapsulation in polylactic-co-glycolic acid (PLGA) nanoparticles. The particle size analysis indicated a unimodal particle size distribution in all systems, with a mean diameter of 160-170 nm, except for insulin nanoparticles, which showed a smaller particle size. The results of the encapsulation efficiency analysis demonstrated that more lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the problems of drug leakage to the external medium, resulting in improved drug content in the nanoparticles. In spite of the fact that valproic acid is a liquid that is very sparingly soluble in water, very low encapsulation efficiency was obtained. Ketoprofen, a drug sparingly soluble in water, demonstrated intermediate values of encapsulation that were well correlated with its intermediate lipophilicity. More hydrophilic drugs, such as vancomycin and phenobarbital, were poorly encapsulated in PLGA nanoparticles. Insulin was preferentially surface bound on the PLGA nanoparticles. However, a strong hypoglycemic effect of the insulin was observed after administration of the suspension of PLGA nanoparticles with surface-bound insulin to the ileum loop of male Wistar rats.