Formation and Characterization of Vitrified Cellulose Layer around Nanoparticles

Abstract

Cellulose derivatives function as barriers in packaging and wrapping films. This thesis focuses on the formation and characterization of a cellulose layer around encapsulated lumefantrine (LUM). Lumefantrine is a hydrophobic BCS (Biopharmaceutical Classification System) class II drug, which has poor bioavailability within the body. Through FlashNanoPrecipitation (FNP) lumefantrine is encapsulated by the amphiphilic stabilizer HPMCAS into nanoparticles to improve its dissolution kinetics. HPMCAS (hydroxypropyl methylcellulose acetate succinate) is a cellulose derivative. Surprisingly, an unexplained phenomenon was observed with the addition of a high concentration of base to the nanoparticles and subsequent spray drying. When regular LUM-HPMCAS nanoparticles encounter tetrahydrofuran (THF), HPMCAS is dissolved from the particle surface and the LUM is subsequently dissolved. This was not the case with the base treated LUM-HPMCAS nanoparticles; instead, the LUM was protected from the THF.

In this thesis, these THF-protected nanoparticles are generated to understand the mechanism behind their formation and to explore this phenomenon in more detail. The nanoparticles were characterized through dynamic light scattering (DLS), zeta potential measurements, differential scanning calorimetry (DSC), and hydrogen nuclear magnetic resonance spectroscopy (HNMR). After a review of the data, we suggest that a vitrified layer of HPMC is formed around the encapsulated lumefantrine after treatment and drying. This vitrified layer provides protection of the LUM core from THF; the protective ability of this layer coupled with its formation in a nanoparticle has strong implications in forming barriers and films at the nanoscale for both biological and chemical reactions.