Pharmaceutics

Advances in kidney organoid technologies have expanded opportunities to model human renal development, disease, and therapeutic response. Yet pluripotent stem cell-derived organoids remain limited by cellular heterogeneity, incomplete tubular maturation and low scalability, restricting their translational relevance. Tubular-specific organoids, derived from adult kidney epithelium, address many of these constraints by providing stable, reproducible cultures enriched for functional proximal and distal tubular cells. Their polarized transport, metabolic activity and patient-specific phenotypes enable high-fidelity modeling of acute and chronic tubular disorders, nephrotoxicity, and inherited tubulopathies—areas where conventional animal and cell-line models often fall short. In this Perspective, we outline recent advances that position tubuloids as a versatile platform for drug screening, toxicity testing and personalized disease modeling. We highlight emerging integration with microfluidics, biomaterials, and gene-editing strategies that promise greater physiological realism and precision therapeutics. We also discuss persistent barriers that impede broader adoption and clinical translation. We propose a roadmap for advancing tubuloid technologies toward precision nephrology and their future incorporation into diagnostic, pharmacological and regenerative pipelines.

We introduce the Onco-Hem Connectome (OHC), a patient similarity network (PSN) designed to organize real-world hemato-oncology inpatients by exploratory phenotypes with potential clinical utility. Background: Polypharmacy and drug–drug interactions (DDIs) are pervasive in hemato-oncology and vary with comorbidity and treatment intensity. Methods: We retrospectively analyzed a 2023 single-center cohort of 298 patients (1158 hospital episodes). Standardized feature vectors combined demographics, comorbidity (Charlson, Elixhauser), comorbidity polypharmacy score (CPS), aggregate DDI severity score (ADSS), diagnoses, and drug exposures. Cosine similarity defined edges (threshold ≥ 0.6) to build an undirected PSN; communities were detected with modularity-based clustering and profiled by drugs, diagnosis codes, and canonical chemotherapy regimens. Results: The OHC comprised 295 nodes and 4179 edges (density 0.096, modularity Q = 0.433), yielding five communities. Communities differed in comorbidity burden (Kruskal–Wallis ${\epsilon }^2$: Charlson 0.428, Elixhauser 0.650, age 0.125, all FDR-adjusted p < 0.001) but not in utilization (LOS, episodes) after FDR (${\epsilon }^2$ ≈ 0.006–0.010). Drug enrichment (e.g., enoxaparin $\Delta$ = +0.13 in Community 2; vinblastine $\Delta$ = +0.09 in Community 3) and principal diagnoses (e.g., C90.0 23%, C91.1 15%, C83.3 15% in Community 1) supported distinct clinical phenotypes. Robustness analyses showed block-equalized features preserved communities (ARI 0.946; NMI 0.941). Community drug signatures and regimen signals aligned with diagnosis patterns, reflecting the integration of resource-use variables in the feature design. Conclusions: The Onco-Hem Connectome yields interpretable, phenotype-level insights that can inform supportive care bundles, DDI-aware prescribing, and stewardship, and it provides a foundation for phenotype-specific risk models (e.g., prolonged stay, infection, high-DDI episodes) in hemato-oncology.

Background/Objectives: Oleosomes, plant-derived lipid nanostructures comprising a triacylglycerol core surrounded by a phospholipid monolayer and interfacial proteins, provide sustainable alternatives to synthetic lipid vesicles. This study compares solvent-free aqueous extractions of oleosomes from five nuts (almond, macadamia, walnut, hazelnut, pine) and five seeds (flaxseed, sunflower, hemp, sesame, canola/rapeseed) to understand how botanical origin influences composition and physicochemical behavior. Methods: Oleosomes were isolated using solvent-free aqueous extraction. Extraction yield, lipid content, protein content, particle size, polydispersity, and zeta potential were determined using standard analytical assays and dynamic light scattering techniques. SDS–PAGE was performed to evaluate interfacial protein profiles and oleosin abundance. Results: Extraction yields ranged from 8.4% (flaxseed) to 59.5% (walnut). Oleosome diameters spanned 424 nm to 3.9 µm, and all oleosome dispersions exhibited negative zeta potentials (–26 to –57 mV). SDS–PAGE revealed abundant 15–25 kDa oleosins in seed oleosomes but relatively sparse proteins in nut oleosomes. Seed oleosomes were smaller and exhibited stronger electrostatic stabilization, while nut oleosomes formed larger droplets stabilized primarily through steric interactions due to lower oleosin content. Conclusions: Variation in oleosin abundance and interfacial composition leads to distinct stabilization mechanisms in nut and seed oleosomes. These findings establish a predictive basis for tailoring oleosome size, stability, and functionality, and highlight their potential as natural nanocarriers for food, cosmetic, and pharmaceutical formulations.