Preparation of non-spherical vaterite CaCO3 particles by flash nano precipitation technique for targeted and extended drug delivery

Abstract

An ideal anticancer drug release system is designed to release drugs over a prolonged period while minimizing the initial burst to significantly reduce the side effects and the number of medications. In this study, CaCO3 particles (average diameter 800-1600 nm with PDI < 0.2) aiming at such controlled release system were successfully prepared via Flash Nano Precipitation technique. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were both employed as additives for CaCO3 crystallization to promote the formation of vaterite and convex-disc-shaped CaCO3, and at the same time as stabilizers for CaCO3 particles to control particle growth and avoid particle agglomeration. By using the as-prepared vaterites, a satisfying drug loading capacity (~0.1 mg drug/mg particle) was realized, and prolonged drug release was achieved with a low initial release (< 10% within 1 day at pH = 6.0) and approximately zero-order release kinetics before 36 h (R2 > 0.97) or after 36 h (R2 > 0.99). Besides, by changing the particle size, different drug release kinetics could be achieved while the high drug loading capacity and low initial release were both maintained. The vaterite particles prepared in this work could be a potential candidate drug carrier for extended drug release with minimized initial burst and a constant drug releasing rate.