Preparation of Uniform Nonspherical PLGA Particles in the Nanosize Range by Using a Two-Step Premix Membrane Emulsification Technique

Abstract The shape of polymeric particulate systems is a critical determinant of their in vivo fate, and nonspherical nanoparticles are promising candidates for advanced drug delivery. However, spherical-shaped particles are usually produced by conventional emulsion-based methods due to the spontaneous minimization of interfacial tension. In our previous work, uniform nonspherical poly(lactic-co-glycolic acid) (PLGA) particles in the micro-size range were successfully prepared by a premix membrane emulsification technique with phosphate-buffered saline (PBS) as a deformation inducer. However, it is difficult to produce nanosized nonspherical particles because of the inherent conflict between the reduction of droplet size and emulsion deformation. To overcome this limitation, a two-step premix membrane emulsification strategy was developed in the present study to temporally and spatially decouple emulsion formation from shape deformation. Through optimization employing one-variable-at-a-time (OVAT) and orthogonal experimental design, the influence of key formulation factors, including PLGA concentration, poly(vinyl alcohol) (PVA) concentration, PBS concentration, and oil phase volume, on the shape of the particles was systematically evaluated. Under the optimal conditions, uniform nanorods with minor axes of 331.11 ± 85.90 nm were fabricated, and the rod fabrication yield reached nearly 100%. Paclitaxel, a classical chemotherapeutic drug, was successfully encapsulated into the obtained nanorods without altering their anisotropic morphology. Furthermore, the drug-loaded nanorods exhibited enhanced in vitro anti-tumor efficacy against A549 lung cancer cells. This methodology provides a facile route for preparing uniform nonspherical PLGA particles in the nanosize range, offering promising applications as drug carriers in nanomedicine.