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.

In the last half-century, the development of biodegradable polyesters for biomedical applications has advanced significantly. Biodegradable polyester materials containing external stimuli-sensitive linkages are favored in the development of therapeutic devices for pharmacological applications such as delivery vehicles for controlled/sustained drug release. These selectively biodegradable polyesters degrade after particular external stimulus (e.g., pH or redox potential change or the presence of certain enzymes). This review outlines the current development of biodegradable synthetic polyesters materials able to undergo hydrolytic or enzymatic degradation for various biomedical applications, including tissue engineering, temporary implants, wound healing and drug delivery.

A new drug-delivery system of polymer nanoparticles (NPs) bearing pinacol-type boronic ester and alkyne moieties displaying triggered self-immolative polymer degradation in the presence of reactive oxygen species (ROS) with the capability of cellular imaging is presented. The NPs specifically release their drug cargo under concentrations of ROS that are commonly found in the intracellular environment of certain tumors and of inflamed tissues and exhibit significant cytotoxicity to cancer cells compared to their non-ROS-responsive counterparts.

The search for new biomaterials intended for biomedical applications has considerably intensified in recent years. Herein, the synthesis and characterization of a new aliphatic biodegradable copolyester named PBS/PBDL (poly(butylene succinate-co-butylene dilinoleate)) is reported. Surfactant-free, narrowly distributed, nanosized spherical particles (R_H < 60 nm) have been produced from the biodegradable material by applying a single-step nanoprecipitation protocol. Their structure was characterized in detail by employing a variety of scattering techniques and transmission electron microscopy (TEM). Combined SLS and DLS measurements suggested that the nanoparticles comprise a porous core conferring a non-compact characteristic. Their porosity enables water to be entrapped which is responsible for their pronounced stability and relatively fast degradation as followed by size exclusion chromatography (SEC). The polymeric nanoparticles could be loaded with the hydrophobic model drug paclitaxel (PTX) with an encapsulation efficiency of ∼95% and drug loading content of ∼6–7% w_drug/w_polymer. The drug release was followed by HPLC and scattering measurements (DLS, SLS and SAXS). The drug encapsulation and release modifies the inner structure of the nanoparticles, which holds a large amount of entrapped water in the drug-free condition. PTX encapsulation leads to replacement of the entrapped water by the hydrophobic model drug and to shrinking of the nanoparticles, probably due to favorable drug–polymer hydrophobic interactions. Cell viability experiments demonstrated that the nanoparticles are biocompatible and non-toxic, making them potentially useful for applications in nanomedicine.