Cucurbitacin I is a hydrophobic molecule that exerts a degree of polarity, which is expected to complicate its loading in PLGA nanoparticles by the classical emulsion solvent evaporation technique. In the current study, variants of emulsion solvent evaporation method were used to prepare PLGA nanoparticles of cucurbitacin: CI-NP1 (single emulsion starting with 1000 μg drug), CI-NP2 (double emulsion starting with 250 μg drug), and CI-NP3 (double emulsion starting with 500 μg drug). On the other hand, CI-NP4 was prepared by nanoprecipitation (starting with 1000 μg drug). In CI-NP1, cucurbitacin I encapsulation efficiency (EE) was 1.29%. The employment of double emulsion, in CI-NP2 and CI-NP3, increased cucurbitacin I EE to 4.8% and 7.96%, respectively. Nanoprecipitation significantly increased the EE of cucurbitacin I to 48.79% in CI-NP4. It is likely that cucurbitacin I escapes with the organic solvent after the emulsification step to the aqueous phase leading to ineffective entrapment in the polymeric matrix. Avoiding emulsification seems efficient in increasing cucurbitacin I disposition in the instantly-precipitating NPs. Therefore, nanoprecipitation method increases cucurbitacin I entrapment in PLGA NPs and possibly other water-insoluble polar drugs.
Keywords: Cucurbitacin I; Emulsion solvent evaporation; Nanoparticles; Nanoprecipitation; PLGA.