Background: Heart failure (HF), as the end stage of various cardiac diseases, alters blood flow to key organs responsible for drug clearance. This can lead to unpredictable and often suboptimal drug exposure, creating a critical need for quantitative tools to guide precise dosing in this vulnerable population. Methods: This study aimed to establish a whole-body physiologically based pharmacokinetic (PBPK) model for characterizing drug pharmacokinetics in both healthy subjects and patients across the HF severity spectrum. Eight commonly used drugs (digoxin, furosemide, bumetanide, torasemide, captopril, valsartan, felodipine and midazolam) for treating HF and its comorbidities were selected. Following successful validation against clinical data from healthy subjects, the PBPK model was extrapolated to HF patients. Pharmacokinetics of the eight drugs in 1000 virtual HF patients were simulated by replacing tissue blood flows and compared using clinical observations. Results: Most of the observed concentrations were encompassed within the 5th–95th percentiles of simulated values from 1000 virtual HF patients. Predicted area under the concentration–time curve and maximum plasma concentration fell within the 0.5~2.0-fold range relative to clinical observations. Sensitivity analysis demonstrated that intrinsic renal clearance, unbound fraction in blood, muscular blood flow, and effective permeability coefficient significantly impact plasma exposure of digoxin at a steady state. Oral digoxin dosing regimens for HF patients were optimized via the validated PBPK model to ensure that steady-state plasma concentrations in all HF patients remain below the toxicity threshold (2.0 ng/mL). Conclusions: A PBPK model was successfully developed to predict the plasma concentration–time profiles of the eight tested drugs in both healthy subjects and HF patients. Furthermore, this model may also be applied to guide digoxin dose optimization for HF patients.

Background: Photostability assessment is a critical component in the development of drug products, particularly for antibody–drug conjugates (ADCs) containing light-sensitive small molecules such as camptothecin (CPT) and its derivatives. ADCs conjugated with CPT derivative payloads often require extensive formulation and drug product development to ensure product stability due to their unique light-induced degradation pathways. In this study, we assessed the photostability of two ADC molecules with a CPT derivative payload (deruxtecan, DXd). Methods: Following light exposure, the stability of ADCs was assessed by examining critical quality attributes, such as aggregation and photodegradation products of the antibody, payload, and formulation excipients, using advanced liquid chromatography and mass spectrometry techniques. Results: Our results revealed key degradation pathways, including the formation of high-molecular-weight (HMW) species, payload degradation, and post-translational modifications (PTMs) on amino acid residues in the antibodies. Additionally, the DXd payload amplified the photosensitivity of the formulation solution, leading to histidine degradation in the formulation buffer and subsequent pH changes. To enhance the stability of ADCs for manufacturing and therapeutic use, we developed a robust formulation by systematic buffer screening and a targeted evaluation of selected antioxidant excipients. Further investigations into light conditions revealed that DXd ADCs are particularly sensitive to short-wavelength light. When evaluating the container closure system, it was demonstrated that using amber vials is a viable option for protecting against light-induced degradation. Conclusions: This report outlines a comprehensive strategy to address photo instability in DXd ADC drug product development, focusing on formulation optimization, controlled manufacturing light settings, and the option of using protective containers to ensure product stability.

Background/Objective: Voriconazole exhibits nonlinear pharmacokinetics and wide interindividual variability driven by CYP2C19 phenotype and clinical covariates, necessitating early therapeutic drug monitoring (TDM). This study aimed to assess how the choice of population pharmacokinetic (PopPK) models influences genotype-stratified voriconazole exposure under a standardized adult regimen, and to delineate model-specific implications for clinical prescribing. Methods: Five CYP2C19-informed PopPK models (Yun, Ling, Wang, Dolton, Friberg) were evaluated under one oral dosing scenario with an identical extensive metabolizers (EM)/intermediate metabolizer (IM)/poor metabolizers (PM) cohort; steady-state exposure metrics were compared across models, with sensitivity checks using model-specific cohorts. Results: Yun predicted the highest exposures with the steepest EM–IM–PM gradient, suggesting a need for caution against upper-tail exceedance when genotype effects are pronounced. Ling yielded intermediate exposures with a modest gradient, consistent with adult central tendencies, thus supporting its use for standard adult initial dosing. Wang primarily distinguished between EM and PM, proving useful for lower-bound checks where underexposure risk or limited genotype information is a concern. Friberg (and Dolton) demonstrated lower exposures with limited genotype separation, offering insights when persistent underexposure is suspected. Conclusions: These model-specific patterns indicate that PopPK model choice can influence initial dose-band selection and the timing of early TDM in routine adult care. Ling can serve as a baseline for standard adult initiation, whereas Yun is appropriate for safety-first scenarios when upper-tail risk from strong genotype effects is anticipated; Wang assists when IM data are lacking or when lower-bound checks are needed. Generalizability beyond standardized adult dosing (e.g., special populations) remains limited.

Quantum dots (QDs) have emerged as promising nanomaterials in cancer therapeutics owing to their tunable optical properties, versatile surface functionalization, and potential for simultaneous imaging and drug delivery. This review focuses on targeted quantum dots (TQDs), highlighting their role in overcoming the limitations of passive drug delivery strategies, such as poor specificity, high systemic toxicity, and limited therapeutic efficacy. We begin by outlining the fundamentals of QDs, including their types, heterostructures, and biomedical formulations. Recent advances in tailoring QD physicochemical properties to the cancer microenvironment are discussed, with emphasis on routes of administration and targeting strategies. The review critically examines different molecular targeting approaches—such as folate receptors, transferrin receptors, aptamers, antibodies, peptides, and hyaluronic acid—used to enhance therapeutic precision. Furthermore, we summarize progress in TQD-based combination therapies, including chemotherapy–photodynamic therapy, photothermal therapy, radiotherapy, and multimodal platforms that integrate therapy with imaging. Special attention is given to the role of QDs in theranostic, hydrogels, nanocomposites, and hybrid systems that enable controlled drug release and real-time monitoring. Despite significant advancements, challenges remain regarding biocompatibility, safety, and regulatory approval. Overall, this review provides an integrative perspective on the design, functionalization, and biomedical applications of TQDs, underscoring their potential to improve cancer treatment outcomes through enhanced specificity, reduced side effects, and multifunctional theranostic capabilities. Highlight of novelty: This review uniquely emphasizes the latest advances in targeted quantum dots (TQDs), particularly in surface functionalization, hybrid nanostructures, biodistribution, and multimodal theranostic applications, providing an updated perspective that extends beyond conventional QD-based cancer therapies.

Objectives: Cyclosporin A (CsA) is an immunosuppressive drug that is highly effective. CsA, similar to other drugs with limited oral bioavailability due to poor membrane permeability, requires the use of absorption enhancers in its formulations. Phe-Cys-Ile-Gly-Arg-Leu (FCIGRL-OH), a peptide fragment of Zonula occludens toxin (ZOT), has been studied for its potential to enhance drug absorption by regulating intercellular tight junctions. This study aimed to evaluate the effects of four novel modified peptides, which have been substituted or dimerized at the C-terminus or cysteine moiety of FCIGRL-OH, as improved versions of FCIGRL-OH on the intestinal permeation of CsA. Methods: The four modified peptides used were FCIGRL-NH2 (Pep-1), homo-dimer peptides derived from FCIGRL-OH and Pep-1 (Pep-2, Pep-3), and a peptide in which the cysteine in Pep-1 was replaced with N3-substituted dipropionic acid (Pep-4). Pharmacokinetic analysis was performed following intraduodenal administration of CsA with each of four peptides in the presence of levan and benzalkonium chloride (BC) in rats. Results: Results showed that each of Pep-2, Pep-3, and Pep-4 significantly increased intestinal absorption of CsA in the presence of levan and BC. In particular, the area under the curve (AUC0–360min) for CsA was significantly enhanced by 2.01-fold (p < 0.01) and 2.03-fold (p < 0.05) when treated with Pep-3 and Pep-4, respectively, at a dose of 10 mg·kg−1. Additionally, the maximum plasma concentration (Cmax) of CsA increased by 2.46-fold (p < 0.01) with Pep-3 and by 2.37-fold (p < 0.01) with Pep-4. Conclusions: These study findings indicate that Pep-2, particularly Pep-3 and Pep-4, are involved in tight junction opening as novel absorption enhancers for intestinal delivery of CsA.

Antimicrobial resistance (AMR) poses an escalating global health crisis, projected to cause up to 10 million deaths annually by 2050. Conventional antibiotics are increasingly ineffective due to microbial adaptation, overuse, and disruption of gut microbiota. Nanotechnology offers promising alternatives, but traditional nanoparticle synthesis often relies on toxic chemicals and energy-intensive processes. This review explores mushroom-derived nanoparticles (myco-NPs) as sustainable, eco-friendly antimicrobials. Edible and medicinal mushrooms contain bioactive compounds, including polysaccharides, flavonoids, and proteins, that act as reducing and stabilizing agents in nanoparticle biosynthesis. Myco-NPs exhibit antimicrobial activity through membrane disruption, oxidative stress, immune modulation, and biofilm inhibition, while also demonstrating synergistic effects with antibiotics and potential roles in regulating the gut microbiota. Recent advances highlight their potential applications in medicine, food safety, and environmental protection. However, challenges remain regarding standardization, safety evaluation, and large-scale production. We emphasize interdisciplinary collaboration as essential to translating mushroom-based nanotechnology into effective clinical and industrial solutions.

Background: Natural compounds such as fisetin have promising in breast cancer treatment, but their poor pharmacokinetics limit their therapeutic application. This study utilized a synergistic approach by combining fisetin-loaded Nigella sativa (N.S.) oil nanovesicles (FIS-NSs) and carbohydrate-based microneedles (FIS-NSs-MNs) to improve breast cancer management. Methods: Chemical composition of NS petroleum ether extract using gas chromatography–mass spectrometry (GC/MS). FIS-NSs were prepared and characterized for particle size, polydispersity, zeta potential, encapsulation efficiency, and stability. These vesicles were embedded into gelatin, hyaluronic acid, and carboxymethyl cellulose microneedles. In vitro drug release, ex vivo permeation, cytotoxicity against breast cancer cells, and in vivo antitumor efficacy in Ehrlich tumor models were evaluated. Results: Optimized FIS-NSs displayed nanoscale size (190 ± 0.74 nm), low P.D.I (0.25 ± 0.07), high surface charge (+37 ± 0.57 mV), and high encapsulation (88 ± 0.77%). In vitro investigations showed sustained FIS release (~85% over 72 h), while ex vivo permeation showed higher absorption than free fisetin. Both FIS-NSs and FIS-NSs-MNs showed dose-dependent cytotoxicity against breast cancer cells, with lower IC50 than free fisetin (24.7 µM). In vivo, FIS-NSs-MNs and tumor burden inhibition (~77%), reduced oxidative stress (54%), restored antioxidant defenses, and decreased inflammatory markers. Immunohistochemical analysis for caspase-3 showed apoptosis activation within tumor tissues. Conclusions: These findings demonstrate that FIS administration via NS-MNs improves drug stability, penetration, and apoptotic activity, resulting in enhanced anticancer effects. This innovative nanovesicle–microneedle platform provides a non-invasive, effective, and patient-friendly approach for the effective treatment of breast cancer, with potential for broader applications in oncological nanomedicine.

Background: Pulmonary administration offers a promising route for certain biologics, particularly when treating respiratory diseases. Spray drying is widely employed to produce inhalable powders with the biologics incorporated in a stabilizing amorphous sugar. Hydrophobic amino acids such as leucine are frequently added to improve dispersibility. Objectives: While the aerodynamic benefits of leucine are well established, its influence on irreversible moisture-induced dry powder particle aggregation and protein stability during storage remains less evaluated. Methods: In this work, inulin-based powders with and without 4 wt-% leucine were spray dried and stored at 43%, 58%, 69%, and 75% relative humidity (RH) at 20 ± 2 °C. Results: Immediately after drying, both formulations displayed comparable physicochemical characteristics. However, during storage of inulin-only formulations, dry powder particles showed viscous flow and formed big irreversible aggregates after storage at an RH of 58% and above, whereas leucine-containing powders remained intact across all tested conditions up to 20 days. Protein stability was assessed using lactate dehydrogenase (LDH) and β-galactosidase (β-gal) as model proteins. At 43% RH, the Tg remained above the storage temperature, and both LDH and β-gal retained their enzymatic activity for up to 20 days. At 75% RH, however, the Tg dropped to below storage temperature, resulting in a loss of stability for LDH, consistent with its reliance on vitrification. In contrast, β-gal maintained its activity at 75% RH, indicative of stabilization through water replacement. Conclusions: Overall, these results demonstrate that leucine enhances the physical stability of inulin powders by preventing irreversible aggregation under humid conditions. However, this effect does not extend to protecting proteins reliant on vitrification. These findings highlight the potential of inulin and leucine to reduce the need for stringent storage conditions of biologics.

Background/Objectives: Ultradeformable liposomes represent an established platform for topical delivery of antioxidant compounds, thanks to their structural flexibility and ability to enhance skin permeation, but standardized manufacturing protocols are still lacking. This study presents a microfluidic-based strategy for the scalable production of ultradeformable liposomes encapsulating Stellaria media extract, a polyphenol-rich phytocomplex with strong antioxidant activity. Methods: Liposomes were produced with a GMP-like microfluidic platform enabling fine control of formulation parameters and high reproducibility under conditions directly transferable to continuous manufacturing. Process optimization tested different total flow rates. Characterization included particle size and distribution, encapsulation efficiency, colloidal stability and kinetics of release. Permeation was assessed with Franz diffusion cells using human stratum corneum and epidermidis membranes. Results: Optimal conditions were a flow rate ratio of 3:1 and a total flow rate of 7 mL/min, yielding ultradeformable liposomes with a mean size of 89 ± 1 nm, a polydispersity index < 0.25, and high encapsulation efficiency (72%). The resulting formulation showed long-term colloidal stability and controlled release. Diffusion studies demonstrated a 2-fold increase in permeation rate compared to the free extract. Conclusions: These findings highlight the potential of microfluidics as a robust and scalable technology for the industrial production of ultradeformable liposomes designed to enhance the dermal delivery of bioactive phytocomplex for both pharmaceutical and cosmeceutical applications.

Background/Objectives: The inherent low aqueous solubility of lipophilic drugs, belonging to Class II based on Biopharmaceutical classification system, negatively impacts their oral bioavailability. However, the manufacturing of pharmaceutical dosage forms for these drugs faces challenges related to environmental impact and production complexity. Herein, the surfactant-enriched cross-linked scaffold addresses the limitations of conventional approaches, such as the use of organic solvents, energy-intensive processing, and the demand for sophisticated equipment. Methods: Scaffold former (Pluronic F68) and scaffold trigger agent (propylene glycol) were used to prepare cross-linked scaffold loaded with candesartan cilexetil as a model for lipophilic drugs. Moreover, surfactants were selected based on the measured solubility to enhance formulation loading capacity. Design-Expert was used to study the impact of Tween 80, propylene glycol, and Pluronic F68 concentrations on the measured responses. In addition, in vitro dissolution study was implemented to investigate the drug release profile. The current approach was assessed against the limitations of conventional approach in terms of environmental and manufacturing feasibility. Results: The optimized formulation (59.27% Tween 80, 30% propylene glycol, 10.73% Pluronic F68) demonstrated a superior drug loading capacity (19.3 mg/g) and exhibited a solid-to-liquid phase transition at 35.5 °C. Moreover, it exhibited a rapid duration of solid-to-liquid transition within about 3 min. In vitro dissolution study revealed a remarkable enhancement in dissolution with 92.87% dissolution efficiency compared to 1.78% for the raw drug. Conclusions: Surfactant-enriched cross-linked scaffold reduced environmental impact by eliminating organic solvents usage and reducing energy consumption. Moreover, it offers significant manufacturing advantages through simplified production processing.