Synthesis of Amphiphilic Amino Poly-Amido-Saccharide and Poly(lactic) Acid Block Copolymers and Fabrication of Paclitaxel-Loaded Mucoadhesive Nanoparticles.

Drug delivery to the esophagus through systemic administration remains challenging, as minimal drug reaches the desired target. Local delivery offers the potential for improved efficacy while minimizing off-target toxicities but necessitates bioadhesive properties for mucosal delivery. Herein, we describe the synthesis of two new mucoadhesive amphiphilic copolymers prepared by sequential ring-opening copolymerization or postpolymerization click conjugation. Both strategies yield block copolymers containing a hydrophilic amine-functionalized poly-amido-saccharide and either a hydrophobic alkyl derivatized poly-amido-saccharide or poly(lactic acid), respectively. The latter resulting copolymers readily self-assemble into spherical, ≈200 nm diameter, positively charged mucoadhesive nanoparticles. The NPs entrap ultrahigh levels of paclitaxel via encapsulation of free paclitaxel and paclitaxel conjugated to a biodegradable, biocompatible poly(1,2-glycerol carbonate). Paclitaxel-loaded NPs rapidly enter cells, release paclitaxel, are cytotoxic to esophageal OE33 and OE19 tumor cells in vitro, and, importantly, demonstrate improved mucoadhesion compared to conventional poly(ethylene glycol)-poly(lactic acid) nanoparticles to ex vivo esophageal tissue.

Assessing the accuracy of a multisection robotic bronchoscope prototype in localization and targeting of small pulmonary lesions.

Objectives: Robotic bronchoscopy (RB) has emerged as a novel technique to address issues with the biopsy of small peripheral lung lesions. The objective of this study was to quantitatively assess the accuracy of a novel multisection robotic bronchoscope compared with current standards of care. Methods: This is a prospective, single-blind, comparative study where the accuracy of a multisection RB was compared against the accuracy of standard electromagnetic navigational bronchoscopy (EM-NB) during lesion localization and targeting. Five blinded subjects of varying bronchoscopy experience were recruited to use both RB and EM-NB in a swine lung model. Accuracy of localization and targeting success was measured as the distance from the center of pulmonary targets at each anatomic location. Subjects used both RB and EM-NB to navigate to 4 pulmonary targets assigned using 1:1 block randomization. Differences in accuracy and time between navigation systems were assessed using Wilcoxon rank-sum test. Results: Of the 40 total attempts per modality, successful targeting was achieved on 90% and 85% of attempts utilizing RB and EM-NB, respectively. Furthermore, RB demonstrated significantly lower median distance to the real-time EM target (1.1 mm; interquartile range [IQR], 0.6-2.0 mm) compared with EM-NB (2.6 mm; IQR, 1.6-3.8) (P < .001). Median target displacement resulting from lung and bronchus deformation during bronchoscopy was found to be significantly lower using RB (0.8 mm; IQR, 0.5-1.2 mm) compared with EM-NB (2.6 mm; IQR, 1.4-6.4 mm) (P < .001). Conclusions: The results of this study demonstrate that the multi-section RB prototype allows for improved localization and targeting of small peripheral lung nodules compared with current nonrobot bronchoscopy modalities.

Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment.

Ex vivo machine perfusion or normothermic machine perfusion is a preservation method that has gained great importance in the transplantation field. Despite the immense opportunity for assessment due to the beating state of the heart, current clinical practice depends on limited metabolic trends for graft evaluation. Hemodynamic measurements obtained from left ventricular loading have garnered significant attention within the field due to their potential as objective assessment parameters. In effect, this protocol provides an easy and effective manner of incorporating loading capabilities to established Langendorff perfusion systems through the simple addition of an extra reservoir. Furthermore, it demonstrates the feasibility of employing passive left atrial pressurization for loading, an approach that, to our knowledge, has not been previously demonstrated. This approach is complemented by a passive Windkessel base afterload, which acts as a compliance chamber to maximize myocardial perfusion during diastole. Lastly, it highlights the capability of capturing functional metrics during cardiac loading, including left ventricular pulse pressure, contractility, and relaxation, to uncover deficiencies in cardiac graft function after extended periods of preservation times (˃6 h).