Antibody–drug conjugates (ADCs) are a rapidly advancing class of targeted cancer therapeutics that couple the antigen specificity of monoclonal antibodies (mAbs) with the potent cytotoxicity of small-molecule drugs. In their core design, a tumor-targeting antibody is covalently linked to a cytotoxic payload via a chemical linker, enabling the selective delivery of highly potent agents to malignant cells while sparing normal tissues, thereby improving the therapeutic index. Humanized and fully human immunoglobulin G1(IgG1) antibodies are the most common ADC backbones due to their stability in systemic circulation, robust Fcγ receptor engagement for immune effector functions, and reduced immunogenicity. Antibody selection requires balancing tumor specificity, internalization rate, and binding affinity to avoid barriers to tissue penetration, such as the binding-site barrier effect, while emerging designs exploit tumor-specific antigen variants or unique post-translational modifications to further enhance selectivity. Advances in antibody engineering, linker chemistry, and payload innovation have reinforced the clinical success of ADCs, with more than a dozen agents FDA approved for hematologic malignancies and solid tumors and over 200 in active clinical trials. This review critically examines established and emerging conjugation strategies, including lysine- and cysteine-based chemistries, enzymatic tagging, glycan remodeling, non-canonical amino acid incorporation, and affinity peptide-mediated methods, and discusses how conjugation site, drug-to-antibody ratio (DAR) control, and linker stability influence pharmacokinetics, efficacy, and safety. Innovations in site-specific conjugation have improved ADC homogeneity, stability, and clinical predictability, though challenges in large-scale manufacturing and regulatory harmonization remain. Furthermore, novel ADC architectures such as bispecific ADCs, conditionally active (probody) ADCs, immune-stimulating ADCs, protein-degrader ADCs, and dual-payload designs are being developed to address tumor heterogeneity, drug resistance, and off-target toxicity. By integrating mechanistic insights, preclinical and clinical data, and recent technological advances, this work highlights current progress and future directions for next-generation ADCs aimed at achieving superior efficacy, safety, and patient outcomes, especially in treating refractory cancers.

Respiratory infections remain a significant global health concern, especially as multidrug-resistant (MDR) respiratory pathogens reduce the effectiveness of conventional antibiotics. Patients with chronic lung diseases face persistent biofilm-related infections that are difficult to treat, underscoring the urgency for new solutions. This challenge has renewed focus on bacteriophage therapy as a promising alternative in respiratory antimicrobial management. Bacteriophages are viruses that selectively infect and lyse bacteria, showing strong potential as a precise and effective therapy for resistant pulmonary infections. This review focuses on the mechanisms of phage biology and therapy in lung infections, highlighting their unique interactions with mucus, surfactants, and immune defenses—all of which are central to their clinical promise. The review examines advances in phage engineering, delivery strategies, and inhaled formulations aimed at maximizing phage stability and targeting within the airways. It summarizes recent preclinical and clinical progress targeting MDR respiratory pathogens and discusses regulatory, manufacturing, and safety considerations key to integrating phage therapy into mainstream respiratory care.

Background/Objectives: γ-Cyclodextrin metal–organic frameworks (γ-CD-MOFs) are biocompatible porous crystalline materials that combine the advantages of both γ-cyclodextrins (γ-CDs) and MOFs, making them promising carriers for drug delivery. However, drug loading efficiencies into γ-CD-MOFs achieved by impregnation method involves complex interactions that necessitate further systematic exploration. This study aimed to determine the impregnation conditions that significantly impact tenoxicam (TNX) loading into γ-CD-MOFs and its aqueous solubility, and to identify the optimal possible conditions for maximizing both. Methods: A three-factor, three-level (3³) Box–Behnken factorial design technique was utilized. Results: Statistical analysis showed that TNX/γ-CD-MOF molar ratio exerted a significant positive effect on drug loading, whereas loading temperature and time have an insignificant effect. Additionally, while loading TNX into γ-CD-MOFs increased its water solubility, variations in the loading parameters did not produce a significant effect on this solubility. The impregnation conditions obtained from the numerical optimization step were a drug/MOF molar ratio of 1.99:1 at 29 ± 0.5 °C for 6 h, which experimentally showed TNX loading of 12.2 ± 1.55%. A discrepancy between the predicted and experimental drug-loading results was observed suggesting that the fitted model does not fully capture the complexity of the system, highlighting the need for experimental verification. Conclusions: This work delivers new insights into the impregnation factors governing TNX loading into γ-CD-MOFs and establishes a foundational framework for the future optimization of CD-MOFs-based drug formulations.

Background: The global rise in antimicrobial resistance (AMR) has created an urgent need for innovative antibacterial strategies and localized delivery systems. This study aimed to develop and characterize electrospun poly (vinyl alcohol) (PVA) nanofibers co-loaded with atorvastatin (ATR) and zinc oxide (ZnO) nanoparticles for use as a multifunctional topical platform for wound healing and infection control. Methods: ZnO nanoparticles were prepared via ball milling and characterized for size and zeta potential. Four PVA-based nanofiber formulations were fabricated using electrospinning: blank (F1), ZnO-loaded (F2), ATR-loaded (F3), and ATR/ZnO co-loaded (F4). The nanofibers were evaluated for morphology, thermal properties, crystallinity, and drug release. Antibacterial efficacy was tested against S. aureus, S. epidermidis, MRSA, and P. aeruginosa using broth microdilution and checkerboard assays. Biocompatibility and wound healing potential were assessed via MTT and fibroblast scratch assays on human foreskin fibroblasts (hFFs). Results: SEM imaging confirmed the production of uniform, bead-free nanofibers. ATR and ZnO nanoparticles were successfully incorporated in the nanofiber. The co-loaded formulation (F4) demonstrated a sustained release profile, releasing approximately 78.7% of ATR over 24 h. While all treatments showed limited activity against P. aeruginosa, the ATR/ZnO co-loaded nanofibers exhibited significantly enhanced antibacterial activity against Gram-positive strains, achieving the lowest MIC values (1.5–2.0 mg/mL). Synergy analysis confirmed an enhanced effect with ATR and ZnO against MRSA. Furthermore, F4 achieved the highest wound closure rate of 92.41% in 24 h while maintaining acceptable cytocompatibility. Conclusions: The integration of ATR and ZnO into PVA nanofibers provides an enhanced antibacterial effect consistent with the synergistic potential observed between free agents targeting Gram-positive wound pathogens. The platform’s ability to simultaneously inhibit bacterial growth and promote rapid fibroblast migration positions it as a promising localized therapeutic for managing infected wounds.

Background: Erectile dysfunction (ED) and premature ejaculation (PE) are prevalent conditions affecting men’s sexual health, for which tadalafil and dapoxetine have shown promise in their treatment, respectively. Conventional oral dosage forms face limitations, including variable absorption and delayed onset of action. In this study, we developed electrospun nanofibers using polyvinylpyrrolidone for buccal drug delivery as an alternative dosage form to oral tablets. This route offers advantages such as easy administration, suitability for those with difficulty swallowing, particularly the elderly, and a rapid onset of action via the blood capillaries, which might improve bioavailability. Methods: PVP nanofibers loaded with tadalafil and dapoxetine were fabricated using a modified electrospinning procedure with the Spraybase system, where an 8% (w/v) PVP ethanol solution containing 1.5% dapoxetine and 0.5% tadalafil was electrospun under controlled conditions (800 µL/h flow rate, 15 cm distance, 0.55 mm needle, and 8–10 kV) to produce uniform fibers. Results: The morphology of the nanofibers was characterized using SEM, revealing smooth, uniform fibers with an average diameter of 218 ± 50 nm for drug-loaded nanofibers. This nanofibrous system also demonstrated ultra-rapid disintegration occurring within 4 ± 1 s and consistent drug loading and encapsulation efficiency for both drugs. The release profile showed a burst drug release after 15 min, which accounted for >45% for tadalafil and >50% for dapoxetine, followed by a sustained increment in the drug release that reached > 60% for tadalafil and >78% for dapoxetine after 30 min until a complete drug release (100%) for both drugs after 180 min. In vitro cytotoxicity studies on human dermal fibroblasts confirmed the safety of both medications, with cell viability exceeding 50%, at concentrations of 1.56 to 25 µg/mL for tadalafil and 4.69 to 9.38 µg/mL for dapoxetine after 24 and 48 h of incubation. Conclusions: These findings highlight the potential of PVP-based nanofibers as a novel buccal delivery system for the combined treatment of ED and PE.

Background/Objectives: Skin wounds interrupt the natural anatomy and function of the skin. The body passes through four physiological phases to repair wounds after injury. Since the fibers are more closely related to the extracellular matrix structure, they can be used as scaffolds to accelerate wound closure. Shikonin is a botanical herbal remedy used as an anti-inflammatory agent and for its wound-healing characteristics. Cresols are known for their bactericidal and fungicidal properties, which promote their utilization as a disinfectant in soap. Therefore, this study aimed to formulate shikonin and cresol-loaded nanofibers for a dual wound-healing and antibacterial wound dressing in vitro. Methods: This study demonstrated the effectiveness of the drug-loaded nanofibers against diverse Gram-positive and Gram-negative bacteria using the minimum inhibitory concentration (MIC) and zone of inhibition assays. Results: Scanning electron microscopy images showed successful formulation of shikonin/cresol fibers with an average diameter of 772 ± 152 nm. The encapsulation efficiency and drug loading for the dual drug-loaded fibers were 44 ± 1% and 25 ± 1 µg/mg, respectively, for shikonin, and 38 ± 1% and 21 ± 0.5 µg/mg, respectively, for cresol, with a full release of both drugs achieved after 180 min. The combination of both compounds exhibited a safe concentration of ≤6 µg/mL, with cell viability of >50% in human dermal fibroblasts (HFF-1) after 24 h. The MIC results indicated that the combination was efficient as an antibacterial agent against Gram-positive bacteria at a safe concentration. The shikonin/cresol-loaded fibrous system showed an inhibition zone close to that of the control drugs, suggesting that the drugs have retained their antibacterial activity after electrospinning. Conclusions: This dual drug-loaded fiber system showed a high potential as an antibacterial wound dressing for skin infection injuries. However, in vivo studies are required to assess the safety and efficacy in an animal model of the dual drug-loaded fiber system.