Search Results (10,017)

The pharmaceutical development of cannabis-based medicinal products is challenged by significant variability in the quality, composition, and standardization of plant-derived active pharmaceutical ingredients (APIs). In Ukraine, despite recent legislative liberalization, a substantial shortage of standardized raw materials continues to limit the development of innovative dosage forms. This study analyses international practices among API manufacturers to identify technological parameters necessary to overcome domestic market barriers and support the implementation of advanced drug delivery systems. Content analysis was conducted on regulatory documentation, professional literature, and manufacturers’ technical specifications. Candidate evaluation followed predefined inclusion and exclusion criteria. The study assessed compliance with Good Manufacturing Practice (GMP) requirements, extraction and purification technologies, the extent of analytical characterization, and batch-to-batch reproducibility. Purposive sampling enabled a comparative analysis of various technological approaches. Marked heterogeneity was observed in API standardization and analytical control indicators among manufacturers. Possession of a GMP certificate was found necessary but may be insufficient to ensure the pharmaceutical equivalence of materials. Differences in extraction methods and purification levels may affect stability profiles, pharmaceutical development strategies, and risk management related to final product quality. The findings demonstrate that manufacturer selection is a critical decision point in pharmaceutical development, with substantiated supplier choice directly influencing dosage form development and regulatory compliance. Full article

Polymer-based dressings constitute an important class of macromolecular biomaterials enabling controlled drug delivery and enhanced wound healing performance. This review summarizes recent advances in the design, fabrication, and functionalization of polymer dressings, with emphasis on natural and synthetic polymer systems applied in biomedical topical and transdermal drug administration. Key material properties, including biocompatibility, mechanical stability, porosity, and degradation behavior, are discussed in relation to drug loading capacity and release kinetics. Current fabrication strategies, such as electrospinning, hydrogel formation, casting, and multilayer assembly, are critically evaluated with respect to structural control and scalability. Particular attention is given to antimicrobial and stimuli-responsive platforms capable of dynamic interaction with the wound microenvironment. Furthermore, challenges related to long-term stability, regulatory requirements, and clinical translation are addressed. By integrating recent experimental findings, this review highlights essential structure–function relationships governing polymer dressing performance and provides design guidelines for next-generation macromolecular topical and transdermal care systems with improved multifunctionality and clinical applicability. Full article

The development of biocompatible functional nanostructures has emerged as a key driver in advancing nanomedicine, environmental remediation, and sustainable energy technologies. However, conventional synthesis methods often rely on toxic reagents, hazardous solvents, and energy-intensive processes, raising significant concerns regarding environmental impact and biological safety. In this context, green synthesis has gained increasing attention as a sustainable alternative, utilizing biological systems, renewable resources, and environmentally benign solvents to produce functional nanomaterials. This mini-review provides an overview of recent advances in the green synthesis of organic, inorganic, and hybrid nanostructures, highlighting their physicochemical properties and functional performance. Particular emphasis is placed on their applications in nanomedicine, including drug delivery, bioimaging, antimicrobial and anticancer therapies, and theranostic platforms. Additionally, their roles in environmental applications, such as pollutant degradation and water treatment, and in energy-related systems, including catalysis, solar energy conversion, and energy storage, are discussed with selected representative examples. Despite significant progress, key challenges remain, including limited mechanistic understanding, reproducibility issues, scalability constraints, and uncertainties related to long-term toxicity and environmental impact. Addressing these limitations will be essential for the safe and large-scale implementation of green nanotechnology. Overall, the integration of green chemistry principles with advanced nanomaterial design offers a promising pathway toward the development of multifunctional, sustainable, and high-performance nanostructures capable of addressing global health, environmental, and energy challenges. Full article

Cataract remains the preeminent cause of reversible blindness globally, with cataract extraction and intraocular lens (IOL) implantation serving as the definitive surgical intervention. Nevertheless, its long-term efficacy is undermined by formidable postoperative complications, specifically posterior capsule opacification (PCO) and endophthalmitis, which necessitate effective prophylactic strategies. IOL modification has emerged as a pivotal paradigm to effectively mitigate these complications. Current approaches encompass surface modification, drug delivery IOLs, and photo-responsive IOLs. Driven by the rapid interdisciplinary convergence of materials science, ophthalmology and pharmacology, the field has also evolved to have combined modification strategies and multifunctional systems. This review provides a comprehensive overview of the recent progress in IOL modification for postoperative complication prophylaxis. By categorizing recent advancements into three major types—surface modification, drug delivery systems, and photo-responsive IOLs—we critically evaluate their mechanisms, advantages, and limitations. Furthermore, we offer strategic insights to accelerate the development of IOL modification and bridge the gap between innovation and clinical translation. Full article

The creation of innovative systems that are able to combine diagnosis and therapy is a crucial opportunity in nuclear medicine. Here, we propose a methodological and multiscale approach for the development of a theranostic platform based on AuNRs functionalized with radiopharmaceuticals. AuNRs offer a versatile and effective system due to their unique physicochemical properties and the possibility of surface functionalization with targeting molecules. Within this framework, key challenges include the functionalization of AuNRs to target the cell nucleus, the loading of AuNRs with radiopharmaceuticals, and the investigation of Auger electron emission from AuNRs under gamma irradiation. Multiscale modelling is employed to describe the behaviour of the system within the cellular environment and to predict potential radiobiological enhancement effects, including synergistic interactions between functionalized AuNRs and radiopharmaceutical agents such as ^99mTc-sestaMIBI. The experimental activity includes gamma irradiation studies, along with the structural and physical characterization of nanomaterials and in vitro biological investigations on T98G cells, to evaluate cytotoxicity and metabolic alterations, with the aim of assessing the potential synergistic effects of the combined system. Full article

Four decades have elapsed since orally disintegrating tablets (ODTs) were first formulated as the emulsion/type Lyoc tablet, a porous mass intended to rapidly disperse in saliva. Following the lyophilization process, new formulations of ODTs were designed, intending to make a simpler and more reproducible formulationZydis, LBL-Flash, Quicksolv, and, more recently, Zydis Ultra. Lyophilization is widely recognized as an effective technique for the development of ODTs, due to its ability to produce highly porous structures that enable rapid disintegration and improved patient compliance. However, its advantages should be considered in relation to other manufacturing methods, as each technology presents specific trade-offs in terms of cost, scalability, mechanical strength, drug loading capacity, and process robustness. In line with the modern sustainable and green pharmacy trend, new raw materials have gained attention as excipients for lyophilized ODTs; these materials include certain plant derivatives, but also performant excipients with newly discovered functionalities. At present, a new generation of ODTs is available in the form of Self-Nanoemulsifying Lyophilized Tablets (SNELTs), which bring the advantages of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) into ODTs via the lyophilization method. The technique is mostly applicable to low-solubility drugs formulated as nanoemulsions, which are absorbed onto solid carriers and further lyophilized, forming the final ODT. Despite its limitations (expensive, time-consuming, and high product friability), lyophilization is being continuously developed nowadays, in combination with other techniques (3D printing, mucoadhesion, or electrospinning), building hybrid platforms for the modern ODTs of the future. Full article

Glioblastoma multiforme (GBM) remains the most aggressive and therapeutically intractable primary brain tumor, with many patients experiencing rapid relapse despite maximal surgical resection followed by standard chemoradiation. This persistent failure reflects the convergence of profound tumor-intrinsic genetic heterogeneity and a highly dynamic, spatially structured, and immunosuppressive tumor microenvironment (TME). Together, these forces create strong selective pressures that fuel tumor evolution, intratumoral diversity, phenotype plasticity, diffuse invasion, and robust resistance to therapy. The TME of GBM is orchestrated through a complex interplay between diverse cellular constituents, including tumor-associated macrophages, reactive astrocytes, endothelial cells, pericytes, and GBM stem cells, and non-cellular components such as extracellular matrix remodeling, hypoxia, metabolic and nutrient gradients, and spatially patterned cytokine and chemokine signaling networks. Additionally, heterogeneity in blood–brain barrier (BBB) and blood–tumor barrier (BTB) complicates drug delivery and immune surveillance, reinforcing therapeutic resistance and regional tumor adaptation. Conventional two-dimensional cell cultures and animal models fail to sufficiently capture these multiscale, patient-specific interactions, limiting their translational predictive power. In this narrative review, we synthesize recent advances in GBM organoid technologies as physiologically relevant, three-dimensional platforms that more faithfully recapitulate TME for driving tumor evolution and treatment resistance. We compare complementary organoid strategies, including patient-derived GBM organoids that preserve native cytoarchitecture, cerebral organoid co-culture systems that reconstruct tumor–brain interactions, and advanced platforms incorporating immune and vascular features such as air–liquid interface cultures, microglia-enriched systems, and BBB/BTB-integrated models. Finally, we highlight emerging innovations such as spatial transcriptomics, organoid-on-a-chip systems, live imaging coupled with lineage tracing, genome engineering, and artificial intelligence integration that collectively position GBM organoids at the forefront of precision neuro-oncology, reproducing TME, enabling dynamic mapping of tumor evolution, and accelerating patient-specific therapeutic discovery. Full article

Glaucoma is a collection of disorders that result in permanent vision loss and is characterized by a gradual decline in retinal ganglion cells. While it may not always be high, intraocular pressure (IOP) is the sole risk factor that can be modified according to extensive clinical research. Glaucoma remains the leading cause of irreversible blindness, yet early treatment lowering intraocular pressure is effective in slowing the rate of visual deterioration. Issues like poor absorption, low bioavailability, and short drug resistance time have thus made the management of glaucoma challenging when using conventional ophthalmic drugs. Thus, extensive research has been conducted to explore specific nanodrug delivery systems from various nanocarriers such as nanoparticles, micelles, liposomes and nanofibers, with a focus on systems that have achieved drug release for more than 12 h. These carriers have demonstrated substantial improvements in a lot of the evaluated aspects: enhancing ocular barrier-crossing capabilities, improving bioavailability, prolonging drug release, targeting active tissues of interest, and reducing IOP. This review covers recent developments in nanocarrier ocular delivery systems regarding the management of glaucoma. In this study, the advantages and disadvantages of each system were evaluated and their potential for advancing translation from research to clinic were assessed. Full article

Background/Objective: The introduction of Ketoconazole (KZ, Nizoral^®) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol^® 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the C_max of the lead KZ-NEC formulation (14.4 ± 1.1 μg/mL) was significantly higher (p < 0.05) compared with the marketed cream formulation (10.5 ± 0.5 μg/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections. Full article

Hydration, interfacial interactions, and matrix stability are critical determinants of the mucoadhesive behavior of cellulose-based polymers. In this study, we investigated the physicochemical and mucoadhesive behavior of hydroxypropyl methylcellulose (HPMC), Carbopol 974P NF, and Kollidon VA 64, along with their binary blends (1:1, w/w) in the context of oral mucosal drug delivery. Wettability, surface free energy, mucoadhesion, and hydration-induced morphological changes were systematically evaluated using contact angle measurements, adhesion and water uptake studies, and real-time surface dissolution imaging (SDi2). The investigated systems displayed markedly different water contact angles: HPMC 103.4 ± 2.7°, Carbopol 47.2 ± 2.3°, Kollidon 36.0 ± 1.8°, HPMC:Carbopol 51.3 ± 2.8°, and HPMC:Kollidon 53.9 ± 3.4°. The corresponding surface free energy (SFE) values ranged from 12.0 mJ/m² for HPMC to 70.5 mJ/m² for Kollidon. Experiments were performed under saliva-mimicking conditions containing 0.1% (w/v) mucin. The HPMC:Carbopol blend exhibited superior mucoadhesive performance and mechanical stability compared with HPMC alone or with the HPMC:Kollidon blends. In 2% (w/v) mucin, the HPMC:Carbopol blend reached a mucoadhesive force of approximately 1.35 N, whereas HPMC and HPMC:Kollidon showed lower values of approximately 0.5–0.75 N and 0.60 N, respectively. After 96 h at 85% RH, the swelling index increased from 14.8 ± 0.5% for HPMC to 29.4 ± 0.3% for HPMC:Carbopol. The incorporation of Carbopol increased the polar contribution to the surface free energy of HPMC-based blends and promoted stable gel layer formation, whereas Kollidon-containing systems underwent rapid disintegration and asymmetric deformation. SDi2 imaging showed that the HPMC disk changed proportionally by approximately 18% in both height and width during 12 h, whereas the HPMC:Kollidon disk almost completely dissolved after approximately 6 h. These results demonstrate that rational selection and combination of cellulose-based polymers can be used to control hydration, interfacial properties, and mucoadhesion, with HPMC:Carbopol blends showing strong potential for oral mucosal drug delivery. Full article

The low water solubility of numerous drug candidates and phytochemicals continues to pose a significant challenge in pharmaceutical development, greatly limiting their bioavailability and therapeutic performance. This review presents a detailed overview of formulation strategies aimed at improving the solubility and dissolution of poorly aqueous-soluble compounds. The biopharmaceutics classification system and the relevance of in vitro–in vivo correlation, as well as key challenges in formulation development, are briefed. Solid-state and particle engineering approaches, including micronization, supercritical fluid technology, electrospinning, and cryogenic techniques, are discussed. Extensive critical examination of amorphous solid dispersions and their preparation methods, as well as crystallization inhibition strategies, is covered. Cocrystallization is highlighted as a promising approach, with emphasis on design principles and preparation methods. Various solubilization techniques, such as pH modification, cosolvency, hydrotropy, micellar solubilization, and cyclodextrin-based complexation, including advanced hybrid systems, are also explored. Emerging solvent platforms, such as deep eutectic systems and lipid-based and nanotechnology-driven approaches, are reviewed for their role in improving solubility and drug delivery. Additionally, enabling technologies such as liquisolid systems and hydrophilic polymers are addressed. Despite notable progress, limitations such as scalability, reproducibility, regulatory constraints, and long-term safety persist. Overall, this review provides integrated insights into formulation design approaches to enhance the solubility and therapeutic efficacy of poorly soluble drugs. Full article

Cutaneous leishmaniasis remains a major therapeutic challenge due to drug toxicity, resistance, and limited efficacy against intracellular parasites. This study evaluated the therapeutic potential of nanoformulated Walterinnesia aegyptia (WA) venom using hyaluronic acid-based (WA-HA) and silver-based (WA-Ag) nanoparticles. Nanoparticles were synthesized and characterized by scanning and transmission electron microscopy and energy-dispersive X-ray spectroscopy. The antipromastigote activity of crude WA venom was assessed by MTT assay, and apoptosis induction was analyzed using Annexin V-FITC/propidium iodide flow cytometry. In vivo efficacy was evaluated in BALB/c mice infected with Leishmania major, with outcomes assessed by lesion progression, biochemical markers, histopathology, and PCR-based parasite detection. WA venom exhibited potent dose-dependent cytotoxicity (IC50 = 26.73 µg/mL) and induced predominantly apoptotic cell death. In vivo, nanoformulated WA significantly enhanced therapeutic outcomes compared with crude venom, with WA-HA achieving near-complete lesion resolution comparable to Amphotericin B. Treatment also reduced parasite burden, normalized liver enzyme levels, and restored hepatic and splenic architecture. These findings demonstrate that nanocarrier-based delivery markedly improves the therapeutic performance and systemic safety of WA venom, highlighting its potential as a promising nanotherapeutic strategy for cutaneous leishmaniasis. Full article

Fungal infections represent an escalating global health challenge due to their increasing incidence, the emergence of multidrug-resistant pathogens, and the limited development of new antifungal agents. Therapeutic efficacy is compromised by mutations in drug targets, overexpression of efflux pumps, alterations in the ergosterol biosynthetic pathway, biofilm-associated tolerance, and extensive genomic plasticity. The growing prevalence of antifungal resistance and the limited availability of effective therapeutic options highlight the urgent need to strengthen epidemiological surveillance and accelerate research into innovative therapeutic strategies. In this review, we discuss the potential of lipid-based drug delivery systems (LDDSs) as a versatile strategy to optimize antifungal administration and overcome resistance mechanisms. Liposomes (LPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoparticles (LNPs) offer high biocompatibility, efficient encapsulation of hydrophobic compounds, structural stability, and controlled drug release. Their nanoscale properties facilitate penetration into biofilms, promote intracellular uptake, and reduce the impact of efflux-mediated drug extrusion, thereby improving cellular penetration and circumventing resistance pathways. In addition, LDDSs increase bioavailability, reduce toxicity, and promote drug accumulation within poorly accessible tissue compartments. Overall, LDDSs represent a promising approach to expand the therapeutic arsenal against both superficial and invasive fungal infections, particularly those caused by multidrug-resistant pathogens. Full article

Glioma, the most common and aggressive primary brain tumor, presents significant clinical management challenges due to difficulties in blood–brain barrier penetration, high tumor heterogeneity, and susceptibility to drug resistance and recurrence, leading to an extremely poor prognosis. Traditional Chinese Medicine (TCM), particularly its derived active ingredients and herbal formulations, with its advantages of multi-component, multi-target, and holistic regulation, demonstrates significant potential in the comprehensive treatment of this disease. This review systematically outlines the research progress in TCM for combating glioma. Regarding mechanisms of action, active TCM components not only directly inhibit tumors by inducing cell apoptosis but also exert synergistic therapeutic effects via multiple pathways. These include remodeling the immunosuppressive microenvironment, activating novel cell death programs such as ferroptosis and immunogenic cell death, intervening in tumor metabolic reprogramming, and reversing chemotherapy resistance. In terms of overcoming delivery barriers, drug delivery systems represented by nanocarriers, liposomes, and extracellular vesicles, combined with the penetration-enhancing effects of aromatic orifice-opening herbs (a class of TCM medicinals traditionally used to “open the orifices” and awaken the mind, now recognized to transiently enhance BBB permeability), have significantly improved the brain-targeting efficiency and bioavailability of TCM components. For clinical translation, a number of innovative drugs derived from TCM, such as elemene, cinobufagin, and ACT001, are currently under clinical investigation, with initial results showing efficacy in prolonging survival and improving quality of life. In the future, by integrating the analysis of multi-target synergistic mechanisms, promoting the clinical translation of intelligent drug delivery systems, and conducting high-quality clinical research on integrated Chinese and Western medicine, TCM is expected to provide a new generation of integrated treatment strategies for glioma that combines holistic and precision medicine. Full article

Background: Baicalein (BA) is a poorly soluble flavonoid with limited oral bioavailability. This study aimed to enhance the solubility and nasal absorption of the compound using a dual-carrier system that combines cyclodextrin inclusion complexes and thermosensitive hydrogels. Methods: The inclusion complexes of BA with hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutyl-β-cyclodextrin (SBE-β-CD), namely BA-HP-β-CD and BA-SBE-β-CD, were prepared via solution stirring and characterized by solubility, dissolution, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis-differential scanning calorimetry (TG-DSC), and Madin-Darby canine kidney (MDCK) cell permeation. The optimal complexes were incorporated into chitosan/β-glycerophosphate thermosensitive hydrogels (BA/HP-Gel and BA/SBE-Gel), followed by evaluations of gelation properties, in vitro release, and in vivo pharmacokinetics in rats. Results: The water solubility of BA-HP-β-CD and BA-SBE-β-CD increased 572 and 582 times, with MDCK permeability enhanced by 5.3 and 2.9 times, respectively. Both hydrogels showed rapid solution-gel transition at nasal temperature and sustained release. Following intranasal administration, BA/HP-Gel and BA/SBE-Gel achieved relative bioavailabilities of 623.5% and 697.8%, respectively, compared with BA-Gel. Conclusions: The dual-carrier platform effectively improved BA solubility, permeability, and nasal bioavailability, offering a promising strategy for nasal delivery of poorly soluble drugs. Full article