Development of a size-tunable paclitaxel micelle using a microfluidic-based system and evaluation of its in-vitro efficacy and intracellular delivery

Abstract

Many challenges still remain for the successful translation of nanodelivery systems from the discovery to clinical practice. The primary concerns include easy scale-up process, uniformity, low size variation, and the ability to control critical physicochemical properties, including size and shape. In the current study, we have developed an easy-to-scale, size-tunable polymeric micelle formulation of paclitaxel using Soluplus, an amphiphilic graft copolymer with the help of a microfluidic platform. Two variable-sized polymeric micelles, ~90 nm, and ~180 nm were prepared by the variation of the drug: polymer ratio. Physicochemical characterization of the micelles was performed in terms of size, polydispersity, solubility, solubility factor, drug loading, and drug release. In-vitro efficacy was analyzed in terms of cytotoxicity in both 2D and 3D spheroid models, along with penetration of the micelles in the 3D spheroid. Intracellular uptake and lysosomal colocalization were also studied. Results demonstrated that the smaller micelles have better encapsulation efficiency with controlled drug release and enhanced cytotoxicity in both 2D and 3D models. Cellular internalization studies indicated that the smaller micelles have higher cellular uptake. In the 3D spheroid model, the smaller micelles exhibited almost complete penetration in 24 h, whereas the larger micelles showed negligible penetration. Altogether, this study indicated that this process could be used for the development of clinically successful nanoformulations.