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

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.