Search Results (1,505)

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality that enables tumor-targeted cell killing. The nuclear capture reaction between boron-10 (¹⁰B) and low-energy thermal neutrons produces high linear energy transfer (LET) particles (α-particles and recoiling lithium nuclei), each of which have short path lengths within the diameter of a single mammalian cell. The deposited energy creates clustered DNA double-strand breaks that are cytotoxic in these tumor cells while sparing the surrounding healthy tissues. This advantage makes BNCT a highly attractive treatment modality compared to conventional radiotherapy. Nevertheless, despite its theoretical precision, the clinical translation of BNCT remains constrained by suboptimal tumor-selective boron delivery; insufficient intracellular accumulation; and heterogeneous biodistribution profiles associated with conventional small-molecule-based boron agents, such as boronophenylalanine (BPA) and sodium borocaptate (BSH). While the development of new accelerator-based neutron sources (ABNSs) has renewed interest in BNCT, effective ¹⁰B delivery remains a major challenge. To address this, nanomedicine has been steadily on the rise in cancer research. In recent years, nanocarrier-based delivery systems have emerged as a transformative alternative delivery strategy. Nanodrugs offer several advantages over conventional small-molecule drugs, such as improved solubility, increased plasma half-life, enhanced permeability and retention in tumors, and active targeting, as well as decreased systemic toxicity and drug resistance. In recent years, nanocarrier-based delivery systems have emerged as a transformative strategy for ¹⁰B delivery. In this focused review, we will discuss various types of nanocarriers used for boron drug delivery that enhance boron loading efficiency and evaluate what enables their selective delivery to and accumulation within tumor cells. Full article

Understanding mass transport of structurally different drugs within ionically crosslinked hydrogel networks remains an important challenge in polymer-based delivery systems. In this study, hydrophilic amoxicillin (AMOX) and amphiphilic doxycycline (DOX) were encapsulated into calcium–alginate beads, respectively. A three-factor and three-level Box–Behnken design was utilized to examine the influences of alginate concentration (2–5%, w/v), CaCl₂ concentration (1–3%, w/v), and gelation time (15–45 min) on encapsulation efficiency (EE). EE exhibited considerable variability for both AMOX (10–86%) and DOX (10–63%). Optimal EE values were achieved at almost 3.5% alginate and 3% CaCl₂. The optimized gelation times differed between AMOX (45 min) and DOX (15 min), which is likely associated with differences in their physicochemical properties, although additional intermediate gelation times could further refine the optimal conditions. ANOVA identified CaCl₂ concentration and the quadratic effect of alginate as the most influential parameters. Furthermore, both models demonstrated robust predictive capability (R² > 0.98). In vitro release experiments demonstrated minimal drug diffusion in simulated gastric fluid (SGF) and significantly accelerated release in simulated intestinal fluid (SIF). These findings indicate a pH-responsive release behavior under simulated gastrointestinal conditions. The release profile was best represented by Higuchi and Korsmeyer–Peppas kinetic models. SEM and optical microscopy revealed uniform spherical beads with drug-dependent microstructural differences: hydrophilic AMOX produced smoother, wrinkled surfaces, whereas amphiphilic DOX induced localized cracking and heterogeneous microdomains. Furthermore, DLS and zeta potential measurements of the released fractions indicated nanoscale particle populations (≈190–225 nm) with moderate negative surface charge (≈−21 mV), suggesting stable colloidal dispersion during intestinal-phase release. Full article

Pulmonary drug delivery has become a vital route for both local and systemic treatments because of the unique structure and function of the respiratory system. Unlike oral and injectable dosage forms, inhalation offers a non-invasive, direct route to deliver medicines to the lungs, bypassing gastric degradation and first-pass hepatic metabolism. Common forms such as aerosols, solutions, suspensions, and dry powders are frequently used to treat respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). However, their effectiveness is often limited by physiological and biopharmaceutical barriers, such as mucociliary clearance, enzymatic degradation, and nonspecific deposition, which reduce drug retention and bioavailability. These issues are especially critical for poorly soluble or sensitive molecules, leading to lower drug concentrations at the target site and necessitating frequent dosing. To address these challenges, advanced nanoparticle-based delivery systems are being developed to improve drug stability, targeting, and controlled release within the lungs. At the same time, computational methods, including deposition modeling, physiologically based pharmacokinetic (PBPK) simulations, and AI-driven optimization, are increasingly used in formulation development to predict in vivo performance and boost translational success. This review covers the physiological and biological barriers to pulmonary drug delivery, explores major inhalation routes and dosage forms, and discusses new therapeutic strategies and nanoparticle platforms. It also highlights the growing role of in silico modeling and AI in accelerating the design and optimization of pulmonary treatments, while addressing current challenges, limitations, and regulatory issues in translating pulmonary nanomedicine into clinical practice. Full article

Microfluidic diffusion systems provide a powerful in vitro platform for evaluating transdermal drug delivery (TDD), yet their predictive capability is often constrained by limited experimental datasets and nonlinear transport behavior across membrane—device configurations. This study integrates machine learning (ML) with microfluidic experimentation to develop accurate and generalizable surrogate models for cumulative drug permeation under different hydrodynamic and membrane conditions. This work presents an ML-augmented microfluidic TDD framework for predicting cumulative drug permeation from small experimental datasets. Caffeine cream permeation was examined across twelve device—membrane configurations (sMDC, mMDC, and LiveBox2 paired with PET, CA, rat skin, and alginate) at three perfusion flow rates. For each configuration, SVR, MLP, RFR, GBR, XGB, and KNN models were trained and cross-validated using only 33 experimental measurements. SVR showed the strongest overall performance among the evaluated models, achieving test R² values typically above 0.97 and RMSE values of <1–3 µg/cm², accurately capturing the nonlinear time-flow-cumulative mass behavior of TDD profiles. A domain-bounded Gaussian-noise augmentation strategy was used to increase local sampling density while keeping augmented values within the experimentally observed time and cumulative-mass ranges. Polynomial equations were obtained from the predictions of SVR to capture the interaction between inputs and outputs. The trained SVR surrogates were then used for automated steady-state identification and surrogate-based operating-point selection, revealing the dependence of the selected flow rate on membrane permeability and device geometry. Alginate consistently delivered the highest steady-state cumulative mass across all systems (up to ~448 µg/cm²), establishing it as the most efficient TDD membrane among those evaluated. Finally, compact third-degree polynomial equations were derived from the SVR predictions, enabling explicit analytical prediction and rapid design-space exploration. Overall, these ML-derived models and analytical equations provide a fast, low-cost tool for predictive design, enabling rapid microfluidic system evaluation and operating-condition selection, and significantly accelerating the development and screening of next-generation TDD platforms. Full article

Background: Cyclodextrin (CD) polymers have attracted increasing attention due to their favourable drug delivery properties and broad pharmaceutical applicability. While the bioavailability and biological behaviour of native cyclodextrins have been extensively investigated, considerably less information is available regarding modified cyclodextrin polymers. Therefore, the present study aimed to investigate the permeation and cellular uptake of an epichlorohydrin-crosslinked β-cyclodextrin polymer using multiple in vitro and ex vivo models. Methods: Fluorescently labelled β-cyclodextrin polymers were applied in all experiments. Membrane permeation studies were performed using an in-line diffusion cell system with membranes of different pore sizes. In vitro transport and cellular uptake were investigated on HaCaT, Caco-2, and TR146 cell monolayers, while ex vivo permeation studies were carried out using skin, buccal, and intestinal tissues. Results: The results demonstrated a strong size-dependent transport behaviour across synthetic membranes. Cell monolayer studies revealed cell-line-dependent differences in polymer intracellular distribution. Lysosomal accumulation was observed in HaCaT and Caco-2 cells, whereas no intracellular accumulation was detected in TR146 cells. These findings suggest differences in polymer permeation among the investigated cell models. Ex vivo studies demonstrated the tissue permeation of cyclodextrin polymers, with marked accumulation within skin layers, indicating predominant dermal retention. Furthermore, strong correlations were identified between the in vitro and ex vivo skin and intestinal models. Conclusions: Overall, the findings demonstrate that β-cyclodextrin polymers exhibit complex, barrier-dependent transport behaviour across different biological models. The observed differences in permeation and intracellular localization suggest that multiple transport processes may contribute to their biological interactions, which provide a foundation for future studies aimed at elucidating the molecular mechanisms governing polymer uptake and permeation. Full article

Ischemic priapism, the most prevalent subtype, constitutes over 95% of all priapism cases, with an estimated annual incidence of 5.34 per 100,000 men in the United States. Characterized by impaired venous outflow and reduced cavernosal blood flow, it is commonly confirmed through cavernous blood gas (CBG) analysis. Notably, ischemic priapism occurs in approximately 33% of men with sickle cell disease (SCD). Standard pharmacological management includes penile aspiration combined with intracavernosal injection (ICI) of sympathomimetic agents such as phenylephrine and etilefrine. These therapies encounter several challenges, including ineffectiveness, off-target effects, and possible complications such as pain, penile fibrosis, and deformities. This highlights the need for novel treatment options. Although pharmacological treatments and surgical procedures are available, there is still a significant demand for novel therapies due to the complexities associated with ischemic priapism and its underlying pathophysiology. This review aims to evaluate the potential of novel therapies as modalities for managing ischemic priapism. By utilizing various treatment modalities, it is possible to achieve localized and targeted action, enhanced safety, minimal off-target effects, and improved patient compliance. Furthermore, this review will explore the potential integration of new drug delivery systems for the management of ischemic priapism. Full article

Cutaneous leishmaniosis (CL) remains a major neglected tropical disease, with current therapies constrained by toxicity, high cost, and variable efficacy. Here, we evaluated an immunochemotherapy strategy combining topical amphotericin B (AmB) with the therapeutic DNA vaccine HisAK70 in a murine model of Leishmania major infection. BALB/c mice were subcutaneously infected and treated with topical AmB cream alone, AmB plus HisAK70, or paromomycin (PM) as a reference therapy. Therapeutic efficacy was assessed through lesion progression, parasite burden in draining lymph nodes and spleen, and immunological markers associated with parasite control. Both PM and the combined AmB + HisAK70 treatment significantly reduced lesion progression and markedly decreased parasite burden compared with infected controls, demonstrating effective control of local infection and systemic dissemination. Importantly, the combination therapy enhanced the efficacy of AmB alone, supporting the beneficial contribution of vaccine-driven immune modulation to therapeutic outcome. Therapeutic efficacy was associated with reduced arginase activity in infected tissues and an increased IFN-γ/IL-4 ratio, indicative of a protective Th1-oriented immune response. Together, these findings highlight immunochemotherapy as a promising strategy for CL treatment, integrating localized topical drug delivery with targeted immune activation to improve therapeutic efficacy while potentially reducing systemic toxicity. Full article

The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid–polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments. Full article

Background: Taurine is a bioactive amino acid that has great potential for wound healing, but it struggles with poor skin penetration and quick clearance. This study aimed to develop taurine-loaded nanoliposomes (Nlp-Tau) to enable sustained local delivery and improve effectiveness. Methods: Nlp-Tau were prepared using thin-film hydration. We characterized them for size, charge, shape, encapsulation efficiency (EE%), loading efficiency (LE%), and in vitro release. Also, its biocompatibility on human foreskin fibroblasts (HFF) with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) has been assessed. In vitro wound healing potential was further evaluated using a scratch assay. Results: Optimized Nlp-Tau showed favorable properties, including an average hydrodynamic diameter of about 282 nm, a polydispersity index of 0.2, a strong negative zeta potential of −31.3 mV, and a spherical shape. However, transmission electron microscopy (TEM) images revealed diameters of about 142 nm and 194 nm for the drug-free and taurine-loaded particles, respectively. Additionally, EE% and LE% were 20% and 2.5%, respectively. In vitro release in PBS (pH 7.4) followed Higuchi kinetics, showing sustained release over 72 h. Nlp-Tau displayed excellent biocompatibility, with HFF viability significantly higher than other groups at concentrations up to 7 mg/mL. Importantly, in the scratch assay, Nlp-Tau treatment resulted in just 6.8% of the wound area remaining after 48 h, which outperformed free taurine at 10.7%. Conclusions: The Nlp-Tau system we developed offers a stable, biocompatible, and effective delivery method for sustained taurine release. It demonstrates greatly improved in vitro wound closure and shows strong potential for future wound care applications. Full article

Introduction: Pain is one of the most common reasons why patients seek medical care, and chronic pain is now recognized as a major health problem worldwide. Better understanding of pain mechanisms has shown the importance of distinguishing nociceptive, neuropathic, and nociplastic pain in order to choose the most effective treatment. In recent years, topical analgesics have gained increasing attention because they can provide pain relief directly at the site of application while reducing systemic exposure and the risk of adverse effects. This is especially important in older adults, patients with multiple diseases, and those exposed to polypharmacy. Methods: This narrative review presents the current knowledge on the pharmacology, efficacy, and safety of topical drugs used in pain treatment. Particular attention is given to topical non-steroidal anti-inflammatory drugs (NSAIDs), lidocaine, capsaicin, menthol, and camphor. The review also discusses newer and less established therapies used mainly in neuropathic pain, including topical ketamine, amitriptyline, phenytoin, gabapentin, and clonidine. A structured, non-systematic literature search was conducted using the PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases to identify studies evaluating the efficacy and safety of topical analgesic therapies. Results: Current evidence supports topical NSAIDs as first-line therapy for localized musculoskeletal pain and osteoarthritis, while lidocaine and high-concentration capsaicin patches are effective options in focal neuropathic pain. Although several newer topical therapies show promising results, more high-quality clinical studies are still needed. Overall, topical analgesia is an important part of multimodal pain management because it combines analgesic efficacy with a better safety profile compared with many systemic therapies. Conclusions: Taking the aspects discussed in this paper into account, it seems justified to search for new drug combinations that would contribute to effective pain therapy with topical agents. It is recognized that a multimodal approach to pain management, which utilizes drugs with different mechanisms of action, can increase efficacy and reduce the systemic adverse events of the drugs used. The effective and safe treatment of patients with pain, especially neuropathic pain, despite emerging new clinical trials, remains a challenge for clinicians. Full article

Background/Objectives: The prevention of sexual HIV-1 acquisition in women and girls in sub-Saharan Africa remains an important public health priority. Expanding the existing biomedical product portfolio to include long-acting vaginal products, such as intravaginal rings (IVRs), is expected to appeal to end users and drive adoption. Methods: We formulated two different triple-combination antiretroviral IVRs, both delivering the acid salt tenofovir (TFV), disoproxil fumarate (TDF), and the free base emtricitabine (FTC), with one delivering elvitegravir (EVG) as the free acid and the other as the sodium salt. The devices were evaluated for pharmacokinetics and local safety in two established preclinical models, sheep and pig-tailed macaques. Results: The IVRs were safe and maintained cervicovaginal fluid (CVF) drug concentrations that were above our efficacy targets derived from prior humanized mouse studies. All three agents were uniformly distributed vaginally, as evidenced by CVF and vaginal tissue measurements. Elevated drug concentrations were observed in macaque vaginal tissue samples collected three days after IVR removal, suggesting a possible forgiveness window. TFV and FTC concentrations in rectal tissue and fluid suggested potential for dual-compartment HIV-1 protection, although the vaginal-to-rectal drug transport mechanism appeared to differ across both species. The humanized mouse vaginal HIV-1 efficacy model was used to empirically compare combination effects when TDF, FTC, and EVG were co-administered, and TDF-EVG was identified as a promising combination to be developed further for IVR delivery in parallel with the triple combination. Full article

Rheumatoid arthritis (RA) is a systemic autoimmune disease in which persistent synovitis drives interconnected cartilage degradation, bone erosion, and functional decline. Conventional synthetic, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) remain the foundation of RA management. Hydrogel-based local therapy should therefore be positioned as an adjunct for selected joints rather than as a substitute for systemic disease control. Hydrogels provide a versatile local materials platform because their injectability, tunable crosslinking, tissue retention, stimulus-responsive release, interfacial adhesion, lubrication, and extracellular matrix-mimetic properties can be tailored to the inflamed joint microenvironment. This narrative, evidence-graded review evaluates local hydrogel therapies using two complementary frameworks: the synovium–cartilage–bone pathological axis and a materials-science chain linking composition and crosslinking to structure and properties, release and degradation, and tissue-level outcomes. Evidence is classified as direct RA evidence, transferable evidence from related disease or tissue-engineering models, or conceptual evidence from mechanistic and materials-science studies. Therapeutic outcomes are separately graded as local immunomodulation, structural protection, tissue repair, or functionally validated structural disease modification. Current preclinical evidence supports the use of hydrogels for sustained local delivery and synovial immunomodulation, while selected systems demonstrate cartilage-protective or anti-erosive effects. However, durable multitissue restoration accompanied by functional recovery remains insufficiently demonstrated. Future studies should prioritize RA-relevant long-term models, in vivo intra-articular pharmacokinetics and biodistribution, standardized structural and functional endpoints, repeat-dose safety, and evaluation as add-on therapy to systemic DMARDs. Full article

Peritoneal metastasis (PM) is the most frequent and lethal pattern of dissemination in gastrointestinal malignancies. Despite advances in systemic chemotherapy, outcomes remain poor because the unique biology of PM, characterized by poor vascularization and the peritoneal–plasma barrier (PPB), limits drug penetration and contributes to treatment resistance. To address these challenges, several locoregional treatment strategies have been developed, including cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). However, their widespread adoption is constrained by invasiveness, strict patient selection, and inconsistent survival benefits. Normothermic intraperitoneal and systemic treatment (NIPS) has emerged as a practical and less invasive alternative, particularly in East Asia. Through an implanted intraperitoneal port, NIPS enables repeated drug administration, providing sustained regional exposure while imposing minimal procedural burden. Importantly, it can be readily integrated with systemic chemotherapy, making it suitable for long-term multimodal treatment. Among available agents, paclitaxel (PTX) is particularly well suited for intraperitoneal administration because of its prolonged retention within the peritoneal cavity and limited systemic absorption. These pharmacokinetic properties allow high local drug concentrations with relatively low systemic toxicity. Consequently, PTX-based NIPS represents a biologically rational and clinically feasible treatment strategy for PM. This review summarizes the pharmacological rationale, clinical evidence, and emerging innovations in drug formulation and delivery that may further enhance the efficacy of PTX-based intraperitoneal chemotherapy for this challenging disease. Full article

Musculoskeletal (MSK) disorders—osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, tendinopathy, and skeletal muscle injury—contribute the largest share of years lived with disability worldwide. Conventional therapy relies on systemic dosing or repeated intra-articular and peri-tissue injections, which suffer from off-target toxicity, poor lesional bioavailability, and low adherence. Polymer microneedles (MNs)—micron-scale projections of biodegradable, dissolving, hydrogel-forming, or composite polymers—have rapidly matured into a versatile platform for minimally invasive, spatially localized, and temporally programmable delivery of small molecules, biologics, nucleic acids, extracellular vesicles, and cells to MSK tissues. This review synthesizes 2018–2026 advances in polymer MN systems engineered specifically for MSK regeneration. We classify dominant polymer chemistries and MN architectures; map fit-for-purpose across bone, cartilage, joint, intervertebral disc, tendon, and skeletal muscle; and survey “smart” MN designs that exploit reactive oxygen species, pH, mechanical, triboelectric, optogenetic, and ultrasonic triggers. We close with a concise conclusion and forward perspective that identifies the key design levers—hybrid MN–scaffold combination products, stimuli-responsive platforms tuned to the MSK micro-environment, and cell- and EV-loaded formats—most likely to have clinical impact. Full article

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized. Full article