Streamlining physiologically-based pharmacokinetic model design for intravenous delivery of nanoparticle drugs.

Physiologically-based pharmacokinetic (PBPK) modeling for nanoparticles elucidates the nanoparticle drug's disposition in the body and serves a vital role in drug development and clinical studies. This paper offers a systematic and tutorial-like approach to developing a model structure and writing distribution ordinary differential equations based on asking binary questions involving the physicochemical nature of the drug in question. Further, by synthesizing existing knowledge, we summarize pertinent aspects in PBPK modeling and create a guide for building model structure and distribution equations, optimizing nanoparticle and non-nanoparticle specific parameters, and performing sensitivity analysis and model validation. The purpose of this paper is to facilitate a streamlined model development process for students and practitioners in the field.

Image-guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies.

While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug-loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size-dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non-invasive in vivo imaging modalities. This allows for visualization and quantification of the whole-body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non-invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state-of-the-art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Thoracoscopic repair for congenital diaphragmatic hernia: lessons from 45 cases.

PURPOSE: To describe the surgical technique, initial results, and overview indications of thoracoscopic repair of congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: A retrospective review was undertaken of patients with CDH who underwent thoracoscopic repair by the same surgeon from January 2001 to January 2005. Patients underwent surgery under general anesthesia. Reduction of the hernia contents was carried out using 1 optical trocar and 2 operating trocars. Pleural insufflation with carbon dioxide was maintained at a pressure of 2 to 4 mm Hg. The hernia defect was repaired using nonabsorbable interrupted sutures with extracorporeal knots. RESULTS: There were 45 patients, including 29 boys and 16 girls. Among 19 newborn patients, there were 13 patients younger than 7 days. The other 26 patients were infants and elders. The hernia was located in the left side in 37 patients and in the right side in 8 patients. The mean operative time was 54 minutes. Conversion was required in 4 patients. There were no complications. However, there were 2 postoperative deaths. CONCLUSIONS: Thoracoscopic repair is feasible and safe for children with CDH, including selective newborn. The technique causes minimal trauma, results in good respiratory function, and promotes early recovery.