Search Results (1,484)

Pediatric drug delivery presents unique challenges due to physiological and pharmacological differences across age groups, requiring specialized formulation approaches beyond simple dose adjustments of adult medications. This review synthesizes recent advances in polysaccharide-based pediatric drug delivery and highlights novel findings that may accelerate clinical translation. It summarizes how chitosan, alginate, hyaluronic acid, dextran, modified starches, and other polysaccharides are engineered into nanoparticles, hydrogels, films, and orodispersible/mini-tablet formulations to improve stability, bioavailability, taste masking, and controlled release across neonates to adolescents. These systems can accommodate developmental variations in absorption, distribution, metabolism, and excretion processes across pediatric subpopulations, with particular emphasis on oral and alternative administration routes. Evidence supporting unexpectedly high acceptability of mini-tablets, successful integration of modified polysaccharides in 3D-printed personalized low-dose therapies, and the emergence of blood–brain barrier-penetrating and RGD-functionalized polysaccharide nanocarriers for pediatric oncology are emphasized as novel, clinically relevant trends. This review also addresses regulatory considerations, safety profiles, and future perspectives. By integrating developmental insights with innovative formulation strategies, polysaccharide polymers offer promising solutions to improve medication adherence, safety, and efficacy across the pediatric age spectrum. Full article

Background/Objectives: Oral administration remains the most widely used route for drug delivery but is unsuitable for many central nervous system (CNS) therapeutics due to extensive hepatic first-pass metabolism and the restrictive blood–brain barrier (BBB). Acetyl salicylic acid (ASA), despite its neuroprotective and anti-inflammatory potential, exhibits poor brain bioavailability when delivered orally, limiting its therapeutic utility in ischemic stroke and chronic neurodegenerative conditions. Methods: This study reports the first use of three-dimensional (3D) bioprinting to develop brain-targeting ASA nanoparticle (NP)-loaded orally disintegrating films (ODFs) for direct systemic uptake and enhanced CNS delivery. The ODFs were fabricated using a CELLINK INKREDIBLE plus^® bioprinter and optimized for uniformity, rapid dissolution, and nanoparticle stability. Results: The films displayed consistent physicochemical properties (weight 10.86 ± 0.28 mg; thickness 0.47 ± 0.26 mm; pH 7.5–7.7) and disintegrated within 2.38 ± 0.28 min. In vitro testing on BEND3 brain endothelial cells confirmed biocompatibility, with no inflammatory response or cytotoxicity up to 62 µg/mL. In vivo biodistribution in murine models demonstrated substantial brain accumulation, achieving 14.15 ng/mg tissue following buccal administration. Conclusions: This work establishes a novel, non-invasive CNS drug delivery platform combining 3D bioprinting with ligand-functionalized ASA NPs to bypass hepatic metabolism and improve brain targeting. The rapid-dissolving ODFs demonstrated high reproducibility, safety, and effective brain deposition, highlighting their translational potential for neurological therapeutics. This approach may be extended to other small molecules with limited CNS penetration, offering a versatile pathway toward precision neuropharmacology. Full article

Cannabidiol (CBD) has transitioned from anecdotal use to an evidence-based adjunctive therapy for Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. This review integrates knowledge on CBD’s pharmacology, pharmacokinetics, and clinical implementation, with focus on metabolism, therapeutic drug monitoring (TDM), and clinically relevant interactions with antiseizure medications. CBD exerts CB1/CB2-independent mechanisms—prominently GPR55 antagonism, TRP-channel desensitization, and adenosine-mediated network dampening—supporting efficacy across heterogeneous seizure phenotypes. Its pharmacokinetic profile is characterized by low and variable oral bioavailability, a pronounced food effect, extensive tissue distribution, and phase I/II biotransformation to the active 7-hydroxy-CBD and abundant 7-carboxy-CBD, resulting in substantial inter-individual variability and liability for drug–drug interactions. Clinically salient interactions include CYP2C19-mediated elevation of N-desmethylclobazam and increased transaminases in valproate co-therapy. We summarize emerging TDM practices—standardized fed-state trough sampling with paired measurement of CBD and 7-hydroxy-CBD—and discuss how preliminary interpretive ranges can support dose optimization, adherence assessment, and safety surveillance. Practical recommendations emphasize interaction-aware titration within evidence-based dose bands, liver function monitoring, and standardized documentation of formulation and sampling conditions. Future work should align pharmacogenomics with TDM, refine bioavailability through advanced delivery systems, and tighten analytical and product-quality standards to consolidate CBD as a precision-ready component of modern epilepsy care. Full article

Background/Objectives: β-galactosidase (lactase) is a transformative enzyme used in many different fields. Its significance spans from biotechnology to food and pharmaceutical industries. β-galactosidase catalyzes the hydrolysis of lactose into glucose and galactose. In medicine, β-galactosidase has gained attention and has many applications, mainly in enzyme replacement therapy. β-galactosidase is the main active ingredient of medications for lactose intolerance. Industrially β-galactosidase is typically produced by the Aspergillus oryzae filamentous fungus. Therapeutic interventions involving β-galactosidase aim to mitigate symptoms and improve the patients’ quality of life. In the food industry, it plays a crucial role in the production of lactose-free products, improving accessibility to dairy products. However, despite its versatility and wide use, challenges connected to β-galactosidase still exist, such as the need for cost-effective and more efficient methods for administering the enzyme. Additionally, there are several ongoing studies that seek to enhance stability and optimize the performance of β-galactosidase in various applications. The aim of this manuscript is to summarize current knowledge about β-galactosidase as an active ingredient and to present some preparations that are commercially available or mentioned in the literature. Methods: A systematic search was conducted in PubMed, Scopus, Embase and Web of Science to identify relevant articles on formulations related to β-galactosidase, focusing on original research articles published between 1895 and 2025 that exclusively examine the use of oral drug delivery. Results: After a rigorous search across multiple databases, 45 relevant studies out of 1633 initial results were selected for analysis. Conclusions: β-galactosidase remains a highly versatile enzyme with broad industrial and medical relevance. While current formulations offer significant benefits, further innovation is needed to improve delivery efficiency, stability, and cost-effectiveness. The findings of this review contribute to a deeper understanding of β-galactosidase as an active ingredient and outline opportunities for advancing its application in oral drug delivery systems. Full article

Microneedle array-based drug delivery offers a minimally invasive and safe approach for breaching the skin barrier, enabling localized and targeted treatment—an advantage particularly valuable in chronic condition management, such as rheumatoid arthritis (RA). RA presents a multifaceted pathophysiology, often necessitating long-term pharmacological management. However, conventional oral administration may lead to systemic drug distribution, increasing the likelihood of adverse effects, and ultimately undermining therapeutic efficacy. In this study, a hollow microneedle array was employed for effective delivery of Tofacitinib and the antioxidant N-acetylcysteine (NAC). A comprehensive evaluation was conducted across multiple levels, in which inflammation and cartilage degradation were assessed histologically using hematoxylin-eosin (H&E) and Safranin O–Fast Green staining. Radiologically, micro-computed tomography (micro-CT) was employed to visualize bone structure alterations. On the molecular level, enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokines and oxidative stress markers. Furthermore, differentially expressed genes and enriched signaling pathways were identified through transcriptomic profiling pre- and post-treatment. And the potential regulatory targets and mechanistic insights into the therapeutic response were elucidated through correlation analyses between gene expression profiles and pathological indicators. This study provides a mechanistic and computational basis for precision targeted therapy, validates the efficacy and safety of microneedle delivery in a rheumatoid arthritis (RA) model, and demonstrates its potential application in local drug delivery strategies. Full article

Oral cancer represents one of the most prevalent malignancies worldwide, characterized by high morbidity and mortality rates primarily due to late diagnosis, limited therapeutic efficacy, systemic toxicity, and recurrence following conventional treatments. Traditional chemotherapeutic drugs, while effective to a certain extent, often suffer from poor bioavailability, nonspecific targeting, and multidrug resistance, highlighting the importance of innovative therapeutic strategies. Nanomedicine has emerged as a promising alternative, providing site-specific delivery, enhanced drug stability, and improved therapeutic outcomes. Among various nanoparticles (NPs), metal oxide nanoparticles (MONPs), such as zinc oxide, titanium dioxide, and copper oxide, have demonstrated potent anticancer activity due to their high surface area, tunable physicochemical properties, and ability to generate reactive oxygen species (ROS). Recent progress in green synthesis approaches, employing plant extracts, microbes, and biopolymers as reducing and stabilizing agents, has further advanced the development of biocompatible and eco-friendly NPs. These green-synthesized NPs minimize toxic byproducts and allow their functionalization with herbal compounds and conventional drugs, offering synergistic effects against oral cancer. This review highlights the limitations of traditional treatments, examines the role of nanomedicine, and discusses the application of green-synthesized MONPs as drug delivery platforms for oral cancer management. It also addresses challenges such as standardization, scalability, safety concerns, and regulatory barriers, while outlining future perspectives that integrate green nanotechnology with precision medicine. Collectively, green nanomedicine offers a sustainable and innovative paradigm with the potential to revolutionize oral cancer therapy. Full article

Introduction: Levodopa (LD) is the most efficacious antiparkinsonian drug. However, long-term conventional LD treatment of Parkinson’s disease (PD) is frequently associated with motor complications. This can be attributed to pulsatile dopaminergic stimulation given the short LD half-life of conventional dosage forms. Tablets capable of delivering more stable and sustained dopaminergic stimulation would better mimic the brain’s natural dopamine activity. Methods: In this study, 3D screen printing technology was used to manufacture oral dosage forms characterized by the sequential release of Carbidopa and Levodopa. This was achieved by separating the two compounds into different compartments within the same dosage form, which were arranged (LXM.5-1) or formulated (LXM.5-2) in a specific way. Both novel dosage forms were compared to conventional immediate release forms such as Sinemet^®. The physicochemical properties of the resulting tablets, LXM.5-1 and LXM.5-2, were assessed in accordance with the USP. Their pharmacokinetic profiles were defined in pigs. Results: The physicochemical properties of LXM.5-1 and LXM.5-2 complied with regulatory requirements. Dissolution studies revealed sequential CD and LD release for both novel dosage forms. They differed regarding the interval between CD and LD release which was shorter for LXM.5-1. PK studies demonstrated that both novel dosage forms exhibited higher LD bioavailability in comparison to Sinemet^®, which was 211.36% and 383.64% for LXM.5-1 and LXM.5-2, respectively. Furthermore, blood levels were more stable and sustained, particularly for LXM.5-2. Conclusions: We conclude that 3D screen-printed LXM.5-1 and LXM.5-2 and variations thereof have the potential to transform the pharmacotherapy of Parkinson’s disease. Full article

Lipid-polymer hybrid nanoparticles (LPHNPs) are the next-generation nanocarriers that integrate the mechanical strength and sustained-release capacity of polymeric cores with the biocompatibility and high drug-loading efficiency of lipid shells. Various design strategies and architectures that enhance encapsulation efficiency, stability, and targeted delivery of diverse therapeutic agents are reviewed. Commonly employed polymers, lipids, and surfactants that enable controlled drug release and enhanced pharmacokinetic performance are summarized in tabular form, while fabrication methods such as single-step, emulsification-solvent evaporation, and microfluidic techniques are discussed for their scalability and reproducibility. The therapeutic potential of LPHNPs in delivering poorly soluble drugs, phytochemicals, and genetic materials achieving synergistic therapeutic outcomes in oncological applications is comprehensively highlighted. The manuscript also includes details on ligand-based functionalization and the integration of imaging and stimuli-responsive elements to enhance targeted delivery and develop multifunctional theranostic LPHNPs systems. Furthermore, non-oncologic applications of LPHNPs in ocular, topical, and oral delivery are discussed, emphasizing their potential in treating inflammatory, infectious, and autoimmune disorders with sustained release and enhanced therapeutic efficacy. Recent patents focusing on improved biocompatibility, dual-drug encapsulation, and mRNA delivery are summarized. However, challenges such as large-scale production, reproducibility, safety, and regulatory standardization must be addressed through quality by design approaches and advanced manufacturing technologies to fully realize the clinical and commercial potential of next-generation LPHNPs. Full article

Gel-based delivery systems have emerged as versatile platforms in dentistry due to their biocompatibility, injectability, tunable rheology, and ability to localize therapeutic agents at the site of application. This review synthesizes current evidence on hydrogels, thermosensitive gels, mucoadhesive gels, nanoparticle-loaded gels, and stimuli-responsive systems, highlighting their structural characteristics, mechanisms of drug release, and clinical relevance. Mucoadhesive formulations demonstrate prolonged retention in periodontal pockets and oral mucosa, improving the efficacy of antimicrobials and anti-inflammatory agents. Thermosensitive gels enable minimally invasive administration and in situ gelation, supporting controlled release at body temperature. Nanoparticle-loaded gels exhibit enhanced drug stability and deeper tissue penetration, while “smart” gels respond to environmental stimuli such as pH or temperature to modulate release profiles. Clinical findings indicate reductions in probing depth, improved wound healing, decreased bacterial load, and better patient comfort when gel systems are used as adjuncts to mechanical therapy or regenerative procedures. However, despite these advances, challenges such as variability in gel stability, manufacturing reproducibility, regulatory approval pathways, and limited long-term clinical evidence still constrain widespread adoption of these systems in routine practice. Full article

Capsaicin, a natural bioactive compound, has attracted wide interest for its potential health benefits. However, its rapid metabolism and strong irritancy upon oral administration have greatly limited its further application. To address these issues, this study developed a nanoparticle delivery system using corn Zein and Brassica rapa L. polysaccharide (BP) as carriers, with capsaicin (CAP) as the core. The optimized formulation (BP:Zein = 1:2, Zein:CAP = 2.5:1, mg/mg) produced stable, uniform spherical nanoparticles with an average particle size of 203.05 nm, a polydispersity index (PDI) of 0.138, a zeta potential of −44.9 mV, an encapsulation efficiency of 54.03%, and a drug loading capacity of 184.57 μg/mg. Fourier transform infrared spectroscopy (FTIR), fluorescence spectroscopy (FS), X-Ray diffraction, scanning electron microscope (SEM), and transmission electron microscopy (TEM) analyses confirmed that CAP was successfully encapsulated, forming nanoparticles through hydrogen bonding and hydrophobic interactions between CAP and Zein. The obtained nanoparticles displayed regular spherical morphology and uniform size distribution. Compared with single-layer Zein–CAP nanoparticles, BP–Zein–Capsaicin (BZC) nanoparticles exhibited markedly improved stability under different pH, ionic strength, and storage conditions. In vitro simulated digestion showed a sustained-release profile, with 36.76% of CAP released after 4 h. The anti-inflammatory experiment showed that both the nanoparticle and free capsaicin groups significantly inhibited xylene-induced acute ear edema in mice, with the medium- and high-dose nanoparticle groups exhibiting stronger anti-inflammatory effects than the free capsaicin group. These findings suggest that the nanoparticle delivery system effectively enhances the anti-inflammatory activity of capsaicin, possibly by improving its stability, achieving sustained release, and enhancing its bioavailability in vivo. Overall, capsaicin-loaded Brassica rapa L. polysaccharide–Zein nanoparticles combine small particle size, high drug loading, and excellent stability, providing a promising strategy for functional food development and targeted bioactive delivery. Full article

Background/Objectives: Kaempferol (KAE) is used to treat gamma radiation-induced damage. However, poor water solubility of KAE restricts its application. Therefore, we developed a KAE-loaded zeolitic imidazolate framework-8 (KAE@ZIF-8) to improve the solubility and bioavailability of KAE, thereby enhancing the radioprotective effect against gamma radiation. Methods: The composite was characterized using scanning electron microscopy (SEM), nitrogen adsorption/desorption analysis, X-ray diffraction (XRD), differential scanning calorimetry (DSC), equilibrium solubility assessments, in vitro release studies, stability evaluations, and drug-loading capacity measurements. The cytotoxic effects of KAE@ZIF-8 on Caco-2 cells were assessed in vitro. Meanwhile, the bioavailability of the preparation was also investigated. Finally, the protective efficacy of KAE@ZIF-8 against total body irradiation was evaluated in C57BL/6 mice. Results: The results indicated that KAE@ZIF-8 was successfully constructed, exhibiting a uniform hexagonal crystal morphology, with KAE transitioning from a crystalline to an amorphous state. As a carrier, ZIF-8 significantly enhanced the solubility of KAE by 9.2-fold, and the cumulative release within 12 h reached approximately 89%. Meanwhile, ZIF-8 could significantly enhance the bioavailability of KAE and reduce its toxicity. We found that pretreatment with KAE@ZIF-8 prolonged mouse survival time after 9 Gy total body irradiation (TBI). Mice were scarified on the 7th day after 7 Gy TBI. Results showed that KAE@ZIF-8 exhibited an improvement of the radioprotective effects, including weight loss mitigation, spleen index increase, radiation-induced intestinal injury attenuation, and modulation expression of IL-1β, IL-6, TNF-α and TGF-β1 following radiation. Conclusions: These results suggest the potential effect of ZIF-8 as an oral drug delivery carrier for radioprotective drugs. Full article

In this study, we review the use of cyclodextrin-based formulations to develop oral tablets of cladribine by enhancing its bioavailability and to improve the solubility and stability of retrometabolic chemical delivery systems (CDSs) in general and estredox, a brain-targeting estradiol-CDS, in particular. Cyclodextrins (CDs), cyclic oligosaccharides that can form host–guest inclusion complexes with a variety of molecules, are widely utilized in pharmaceuticals to increase drug solubility, stability, bioavailability, etc. The stability of the complex depends on how well the guest fits within the cavity of the CD host; a model connecting this to the size of the guest molecules is briefly discussed. Modified CDs, and particularly 2-hydroxypropyl-β-cyclodextrin (HPβCD), provided dramatically increased water solubility and oxidative stability for estredox (estradiol-CDS, E₂-CDS), making its clinical development possible and highlighting the potential of our brain-targeted CDS approach for CNS-targeted delivery with minimal peripheral exposure. A unique HPβCD-based formulation also provided an innovative solution for the development of orally administrable cladribine. The corresponding complex dual CD-complex formed by an amorphous admixture of inclusion- and non-inclusion cladribine–HPβCD complexes led to the development of tablets that provide adequate oral bioavailability for cladribine, as demonstrated in both preclinical and clinical studies. Cladribine–HPβCD tablets (Mavenclad) offer a convenient, effective, and well-tolerated oral therapy for multiple sclerosis, achieving worldwide approval and significant clinical success. Overall, the developments summarized here underscore the importance of tailored cyclodextrin-based approaches for overcoming barriers in drug formulation for compounds with challenging physicochemical properties, and demonstrate the versatility and clinical impact of CD inclusion complexes in modern pharmaceutical development. Full article

Imatinib (IMT) is a small-molecule tyrosine kinase inhibitor that primarily targets platelet-derived growth factor receptor-β and related kinases. Beyond its established efficacy in chronic myeloid leukemia, IMT has also demonstrated therapeutic benefits in gastrointestinal stromal tumors, dermatofibrosarcoma, acute lymphoblastic leukemia, and as a second-line treatment for aggressive systemic mastocytosis or as an anti-Mycobacterium agent. From a physicochemical perspective, IMT exhibits poor aqueous solubility but high membrane permeability, classifying it as a Biopharmaceutics Classification System Class II compound. Pharmacokinetically, IMT shows variable oral absorption and a prolonged terminal half-life, resulting in dose-dependent systemic exposure. Despite relatively high oral bioavailability, its clinical use requires large doses to achieve therapeutic efficacy, underscoring the need for advanced drug delivery strategies. Nano- and microscale delivery systems offer promising approaches to enhance tumor-specific accumulation through the enhanced permeability and retention effect while mitigating resistance mechanisms. However, achieving high drug loading introduces formulation challenges, such as controlling particle size distribution, polydispersity, and scalability. Moreover, designing carriers capable of controlled release without premature leakage remains crucial for maintaining systemic bioavailability and therapeutic performance. Emerging delivery platforms—including polymeric, lipid-based, carbon-derived, and stimuli-responsive nanocarriers—have shown significant potential in overcoming these limitations. Such systems can enhance IMT’s bioavailability, improve selective tumor targeting, and minimize systemic toxicity, thereby advancing its translational potential. This review aims to highlight the different biomedical applications of IMT and off-label uses, and to discuss current advances in drug delivery to optimize its clinical efficacy and safety profile. Full article

Background/Objectives: The aim of this study was to reveal the influence of the natural nanoparticles (Nnps) isolated from Gegen–Qinlian Decoction (GQD), i.e., GQD-Nnps, on the intestinal absorption and pharmacokinetic properties of several representative active GQD constituents. Methods: The morphology of GQD-Nnps was examined using scanning electron microscopy (SEM). Protein and polysaccharide contents were measured using the bicinchoninic acid (BCA) assay and phenol–sulfuric acid method, respectively. Major GQD constituents were quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Formation mechanisms were explored using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and high-resolution mass spectrometry (HRMS). Pharmacokinetic studies were conducted in mice with dextran sulfate sodium (DSS)-induced UC. Results: GQD-Nnps were spherical, with a size of 110.9 ± 8.1 nm and a zeta potential of −13.7 ± 1.5 mV. GQD-Nnps were primarily composed of proteins and polysaccharides. FTIR analysis revealed significant hydrogen bonding interactions between the small molecular and macromolecular constituents of GQD. HRMS analyses indicated complex formation among small molecules, particularly berberine, baicalin, and glycyrrhizic acid. DLS demonstrated good stability of GQD-Nnps in artificial gastric and intestinal fluids. Pharmacokinetic studies showed that, except for puerarin, blood and liver exposure levels of several constituents in the GQD-Nnps group were significantly higher than those in the GQD extract group, suggesting enhanced colonic absorption and hepatic distribution. Conclusions: GQD-Nnps create an oral drug delivery system through complex interactions, significantly enhancing the colonic absorption and hepatic distribution of several active GQD constituents. Full article

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide, with letrozole (LZ) serving as a critical aromatase inhibitor for hormone receptor–positive cases. However, long-term oral administration of LZ is often associated with systemic adverse effects and poor patient compliance. To overcome these limitations, new non-aqueous nanoemulgels (NEMGs) were developed for transdermal delivery of LZ. Methods: The NEMGs were formulated using glyceryl monooleate (GMO), Sepineo P600^®, Transcutol, propylene glycol, and penetration enhancers propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC), and Captex^®. Physicochemical characterization, solubility, stability, and in vitro permeation studies were conducted using Strat-M^® membranes, while in vivo pharmacokinetics were evaluated in rat models. Results: The optimized GMO/PGMC-based NEMG demonstrated significantly enhanced drug flux, higher permeability coefficients, and shorter lag times compared with other NEMGs and suspension emulgels. In vivo, transdermal application of the GMO/PGMC-based NEMG over an area of 2.55 cm² produced dual plasma absorption peaks, with 57% of the LZ dose absorbed relative to oral administration over 12 days. Shelf-life and accelerated stability assessments confirmed excellent physicochemical stability with negligible crystallization. Conclusions: The developed LZ NEMG formulations offer a stable, effective, and patient-friendly transdermal drug delivery platform for breast cancer therapy. This system demonstrates potential to improve patient compliance and reduce systemic toxicity compared to conventional oral administration. Full article