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Background/Objectives: Oral delivery of biologics offers advantages for patient access and adherence compared to injection, but suffers from low bioavailability due to mucosal barriers and drug degradation in the gastrointestinal tract. We previously developed an oral self-pressurized aerosol (OSPRAE) capsule that uses effervescent excipients to generate CO2 gas, building internal pressure to eject powdered drug at high velocity across intestinal mucosa. Methods: Here, we developed two key design improvements: (i) an enteric covering to protect the capsule delivery orifice in gastric fluids and (ii) reduced humidity content of capsules to extend shelf-life. Results: Enteric-covered capsules prevented drug release in simulated gastric fluid and then enabled rapid release upon transfer to simulated intestinal fluid. Burst pressure for enteric-covered capsules was ~3–4 times higher than non-covered capsules. After storage for up to three days, the capsules’ effervescent excipients pre-reacted, making them unable to achieve high pressure during subsequent use. To address this limitation, we prepared capsules under reduced humidity conditions, which inhibited pre-reaction of effervescent excipients during storage, and a polyurethane coating to improve water uptake into the capsule to drive the effervescence reaction in intestinal fluid. Conclusions: These design improvements enable improved functionality of OSPRAE capsules for continued translation in pre-clinical and future clinical development.

Multiplexed imaging techniques require identifying different cell types in the tissue. To utilize their potential for cellular and molecular analysis, high throughput and accurate analytical approaches are needed in parsing vast amounts of data, particularly in clinical settings. Nuclear segmentation errors propagate in all downstream steps of cell phenotyping and single-cell spatial analyses. Here, we benchmark and compare the nuclear segmentation tools commonly used in multiplexed immunofluorescence data by evaluating their performance across 7 tissue types encompassing ~20,000 labeled nuclei from human tissue samples. Pre-trained deep learning models outperform classical nuclear segmentation algorithms. Overall, Mesmer is recommended as it exhibits the highest nuclear segmentation accuracy with 0.67 F1-score at an IoU threshold of 0.5 on our composite dataset. Pre-trained StarDist model is recommended in case of limited computational resources, providing ~12x run time improvement with CPU compute and ~4x improvement with the GPU compute over Mesmer, but it struggles in dense nuclear regions. Quantitative benchmarking shows that pretrained deep learning models outperform classical algorithms for nuclear segmentation, with Mesmer being the top candidate for multiplexed immunofluorescence in translational workflows.

Peanut and tree nut allergies account for most food-induced anaphylactic events. The standard allergy immunotherapy approach involves subcutaneous injection, which is challenging because severe adverse reactions can occur when antigens spread systemically. Allergen localization within the epidermis (i.e., the upper 20–100 µm of skin) should significantly reduce systemic uptake, because the epidermis is avascular. Microneedle (MN) patches provide a convenient method for drug delivery to the skin, but they generally target both epidermis and dermis, leading to systemic delivery. In this study, we adapted MN technology for epidermal localization by performing angled insertion of 250 µm–long MNs that limits MN insertion depth mostly to the epidermis. We designed a biplanar insertion device to aid the repeatability of angled insertions into porcine skin ex vivo at specified angles (90°, 45°, and 20°). When compared to 90° insertions, MN application at 20° decreased mean insertion depth from 265 ± 45 µm to 97 ± 15 µm. Image analysis of histological skin sections revealed that acute-angle insertion increased epidermal localization of delivery for antigen-coated MNs from 25% ± 13% to 70% ± 21%. We conclude that angled insertion of MNs can target antigen delivery to epidermis.