Search

Poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug delivery systems are known to offer a plethora of potential therapeutic benefits. However, challenges related to large-scale manufacturing, such as the difficulty of reproducing complex formulations and high manufacturing costs, hinder their clinical and commercial development. In this context, a reliable manufacturing technique suitable for the scale-up production of nanoformulations without altering efficacy and safety profiles is highly needed. In this paper, we develop an inline sonication process and adapt it to the industrial scale production of immunomodulating PLGA nanovaccines developed using a batch sonication method at the laboratory scale. The investigated formulations contain three distinct synthetic peptides derived from the carcinogenic antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) together with an invariant natural killer T-cell (iNKT) activator, threitolceramide-6 (IMM60). Process parameters were optimized to obtain polymeric nanovaccine formulations with a mean diameter of 150 ± 50 nm and a polydispersity index

Despite the efficacy and potential therapeutic benefits that poly(lactic-co-glycolic acid) (PLGA) nanomedicine formulations can offer, challenges related to large-scale processing hamper their clinical and commercial development. Major hurdles for the launch of a polymeric nanocarrier product on the market are batch-to-batch variations and lack of product consistency in scale-up manufacturing. Therefore, a scalable and robust manufacturing technique that allows for the transfer of nanomedicine production from the benchtop to an industrial scale is highly desirable. Downstream processes for purification, concentration, and storage of the nanomedicine formulations are equally indispensable. Here, we develop an inline sonication process for the production of polymeric PLGA nanomedicines at the industrial scale. The process and formulation parameters are optimized to obtain PLGA nanoparticles with a mean diameter of 150 ± 50 nm and a small polydispersity index (PDI < 0.2). Downstream processes based on tangential flow filtration (TFF) technology and lyophilization for the washing, concentration, and storage of formulations are also established and discussed. Using the developed manufacturing and downstream processing technologies, production of two PLGA nanoformulations encasing ritonavir and celecoxib was achieved at 84 g/h rate. As a measure of actual drug content, encapsulation efficiencies of 49.5 ± 3.2% and 80.3 ± 0.9% were achieved for ritonavir and celecoxib, respectively. When operated in-series, inline sonication and TFF can be adapted for fully continuous, industrial-scale processing of PLGA-based nanomedicines.

Ordered nanofiber arrays are a promising material platform for artificial adhesive structures, tissue engineering, wound dressing, sensor arrays, and self-cleaning surfaces. Their production via self-ordered porous alumina hard templates serving as shape-defining molds is well-established. However, their release requires the destruction of the hard templates, the fabrication of which is costly and time-consuming, by wet-chemical etching steps with acids or bases. We report the nondestructive mechanical extraction of arrays of cross-linked polyacrylate nanofibers from thus recyclable self-ordered nanoporous alumina hard templates. Silica replicas of the latter were synthesized using the extricated nanofiber arrays as secondary molds that could be mechanically detached from the molded material. The approach reported here, which can be combined with microstructuring, may pave the way for the high-throughput production of both functional nanofiber arrays and ordered nanoporous membranes consisting of a broad range of material systems. [ABSTRACT FROM AUTHOR]