Strategies for coupling photon-upconverting nanoparticles with photoactive protein therapeutics

Nanomedicine is a rapidly advancing field as capabilities in nanoscale materials, devices, and sensing grow. Biocompatible nanoparticles have made their way into the pharmaceutical and biomedical market in imaging, diagnosis, targeted drug delivery, and even repair. Similarly, protein therapeutics show promise for their unique combination of high biospecificity and diverse function. This brief perspective explores the merging of these two fields via light-controlled methods mediated by photon-upconverting nanoparticles. The framework of three photoactive protein therapeutic systems will be explored for their integration with upconverting nanoparticles.

Modelling protein therapeutic co-formulation and co-delivery with PLGA nanoparticles continuously manufactured by microfluidics

Formulating protein therapeutics into nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) provides key features such as protection against clearance, sustained release and less side effects by possible attachment of targeting ligands.

Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients

The protein therapeutic and CD95L inhibitor asunercept is currently under clinical investigation for the treatment of glioblastoma and myelodysplastic syndrome. The purpose of this study was to predict the asunercept pharmacokinetics in children and to give dose recommendations for its first use in pediatric glioblastoma patients. A physiologically-based pharmacokinetic (PBPK) model of asunercept in healthy and diseased adults was successfully developed using the available clinical Phase I and Phase II study data. This model was then extrapolated to different pediatric populations, to predict the asunercept exposure in children and to find equivalent starting doses. Simulation of the asunercept serum concentration-time curves in children between 1–18 years of age shows that a dosing regimen based on body weight results in a similar asunercept steady-state exposure in all patients (pediatric or adult) above 12 years of age. For children between 1–12 years, higher doses per kg body weight are recommended, with the highest dose for the very young patients. Translational PBPK modeling is strongly encouraged by regulatory agencies to help with the initial dose selection for pediatric trials. To our knowledge, this is the first report of pediatric PBPK to support the dose selection of a therapeutic protein before its administration to children.

Insights into the Microbial L-Asparaginases: from Production to Practical Applications

L-asparaginase is a valuable protein therapeutic drug utilized for the treatment of leukemia and lymphomas. Administration of asparaginase leads to asparagine starvation causing inhibition of protein synthesis, growth, and proliferation of tumor cells. Besides its clinical significance, the enzyme also finds application in the food sector for mitigation of a cancer-causing agent acrylamide. The numerous applications ensue huge market demands and create a continued interest in the production of costeffective, more specific, less immunogenic and stable formulations which can cater both the clinical and food processing requirements. The current review article approaches the process parameters of submerged and solid-state fermentation strategies for the microbial production of the L-asparaginase from diverse sources, genetic engineering approaches used for the production of L-asparaginase enzyme and major applications in clinical and food sectors. The review also addresses the immunological issues associated with the L-asparaginase usage and the immobilization strategies, drug delivery systems employed to circumvent the toxicity complications are also discussed. The future prospects for microbial Lasparaginase production are discussed at the end of the review article.