Search Results (1,292)

The overactivation of endosomal Toll-like receptor (TLR) in macrophages plays an important role in the pathogenesis of acute lung injury (ALI). There is currently still a lack of nano-formulated and macrophage-targeted endosomal TLR inhibitors that have been approved for clinical uses. We previously discovered that the elevation of endosomal pH using nanodevices provides a promising strategy to specifically inhibit endosomal TLRs in macrophages. The weakly basic drug hydroxychloroquine (HCQ) has been reported for its capability to accumulate in endolysosomes and modulate the acidity in these compartments. To enhance its macrophage-targeting ability and the therapeutic efficacy in vivo, herein we formulated HCQ into a nanoform using liposomes, named HCQ-L. We found that HCQ-L was less cytotoxic and more effective in inhibiting endosomal TLRs (including TLR3, TLR4, TLR 7/8) than the molecular HCQ. Subsequently, a hexapeptide, Pep12, was inserted onto the surface of HCQ-L to form HCQ-L-P12. Interestingly, Pep12 modification significantly improved the stability of liposomes in aqueous solution for at least 2 years; while having enhanced inhibitory effects on TLR7/8 signaling, HCQ-L-P12 displayed similar effects on inhibiting the TLR4 pathway and down-stream pro-inflammatory cytokine production when compared with HCQ-L. Furthermore, both HCQ nanoformulations potently elevated the endosomal pH. In vivo evaluation showed that HCQ-L-P12 and HCQ-L (but not molecular HCQ) were able to alleviate lung inflammation and injuries by decreasing inflammatory cell infiltration upon intratracheal instillation in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. This research provides a new strategy to fabricate lipid-based nanocarriers for targeted delivery of endosomal pH modulators to treat ALI and other acute and chronic inflammatory disorders. Full article

Diacerein is known as a disease-modifying anti-inflammatory drug, primarily used for the treatment of osteoarthritis. Despite its therapeutic potential, the clinical use of diacerein is hindered by poor aqueous solubility, low bioavailability, liver issues, and gastrointestinal side effects, particularly diarrhea. To address these limitations, various innovative pharmaceutical formulation approaches have been explored, including physical modifications, chemical complexation, nanotechnology-based drug delivery systems, and synergistic combination therapies. This review highlights progress in formulation approaches aimed at enhancing the solubility and therapeutic profile of diacerein. Special emphasis is placed on lipid-based carriers, vesicular systems, pH-responsive hydrogels, and dissolving microneedles. Together, these strategies provide a comprehensive platform for the rational design of diacerein formulations, offering promising avenues to overcome its clinical limitations and improve patient outcomes. The insights presented here may also guide the development of more effective delivery systems for other poorly soluble anti-inflammatory agents. Full article

The skin is exposed to many environmental stressors, such as UV rays, pollution, and smoke, and psychological stress, which can compromise its structure and function. These factors can cause premature aging, weaken the skin barrier, worsen or induce pathological conditions such as acne and eczema, hyperpigmentation, and melanoma, and slow healing. Ellagic acid (EA) is a polyphenol with various pharmacological effects important for the treatment of skin conditions. It has antioxidant, anti-inflammatory, and depigmenting properties, and it inhibits the enzyme tyrosinase, involved in melanin production, helping reduce dark spots and exhibiting antiproliferative effects against melanoma cells. With its antioxidant effect, it protects the skin against photoaging, combats oxidative stress and signs of aging, such as wrinkles and loss of elasticity, and strengthens collagen and elastin. However, the main limits of EA are its low aqueous solubility, instability, and poor skin permeability that limit its clinical efficacy. This review focuses on EA formulations developed to overcome these limitations and improve its therapeutic effects for skin diseases. Nano-delivery systems such as vesicles, lipidic and polymeric nanoparticles, nanospheres, cyclodextrins, and nanogels have been reported alongside other innovative preparations such as biscuits, sponges, and nanosheets and conventional ones such as ointments, creams, and films. Full article

Ophthalmic drug delivery encounters unique challenges due to the anatomical and physiological ocular barriers, necessitating the development of novel drug delivery systems (NDDSs). This review focuses on emerging therapeutic platforms, including nanoemulsions (NEs), microemulsions (MEs), self-emulsifying drug delivery systems (SEDDSs) such as self-nano emulsifying drug delivery systems (SNEDDSs) and self-micro emulsifying drug delivery systems (SMEDDSs), emulgels, and in situ-forming emulgels, as novel strategies for enhancing ocular drug delivery. NEs and MEs, due to their small globule size, excellent drug solubility, stability, and bioavailability, offer promising solutions for effective ocular therapy. SEDDSs further enhance the stability and bioavailability of hydrophobic drugs through self-emulsification in aqueous environments. Emulgels, combining the benefits of emulsions and gels, provide sustained and controlled release of therapeutic agents, improving the ocular retention time and therapeutic efficacy. Additionally, in situ-forming emulgels offer the advantage of liquid-to-gel transition upon contact with ocular surfaces, optimizing drug delivery. The review discusses various ocular diseases, challenges for ocular delivery of conventional formulations, updates on emulsion-based novel drug delivery systems for ophthalmic drug delivery, mechanisms of enhanced ocular permeation, formulation strategies, advantages, and challenges, design-of-experiment considerations for optimization, characterizations, and recent advancements in these systems including patents and clinical trials, highlighting their potential for improving the treatment of various ocular diseases. Furthermore, this review explores marketed ophthalmic emulsions and future prospects for integrating these NDDSs into clinical ophthalmology, emphasizing their ability to overcome ocular barriers and enhance therapeutic efficacy. Full article

The progression of atherosclerosis (AS) is strongly linked to lipid crystals accumulation caused by cholesterol metabolism disorders and the worsening of the inflammatory microenvironment. Cyclodextrin (CD), characterized by their unique hydrophobic cavity structure, effectively solubilize cholesterol crystals (CCs) through host–guest recognition and act as a multifunctional nanocarrier core, facilitating synergistic therapy that combines pharmaceutical and adjuvant properties. CD-based nano drug delivery systems (CD-NDDS) enable precise targeting of atherosclerotic plaques. By employing synergistic functions (e.g., CCs solubilization, cholesterol efflux promotion via ABCA1/ABCG1 pathways, inflammasome inhibition, and inflammatory microenvironment alleviation), this system provides an effective strategy for AS therapy. Furthermore, CD-NDDS bestows additional pharmaceutical attributes, including enhanced solubility, controlled release, and responsive stimulation. This review begins by elucidating the intrinsic relationship between cholesterol and AS, followed by an examination of the structure-activity relationship governing CD’s cholesterol adsorption. It then explores the construction strategies, structural characteristics, and targeting mechanisms of CD nanodelivery systems in detail. The work systematically assesses CD’s formulation and pharmacological properties in targeted nanodelivery systems for combating AS, integrating drugs and adjuvants. Finally, future research directions are outlined, addressing biocompatibility optimization, targeting efficiency enhancement, and clinical translation challenges to provide a theoretical foundation and technical guidance for precise AS treatment. Full article

Alzheimer’s disease (AD), the leading cause of dementia, is defined by two pathological hallmarks, amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—both now structurally resolved at near-atomic precision thanks to cryo-EM. Despite decades of research, effective disease-modifying therapies remain elusive, underscoring the need for innovative interdisciplinary approaches. This review synthesizes recent advances in structural biology and nanotechnology, highlighting their synergistic potential in revolutionizing AD diagnosis and treatment. Cryo-EM and NMR have revolutionized our understanding of Aβ/tau polymorphs, revealing structural vulnerabilities ripe for therapeutic targeting—yet clinical translation remains bottlenecked by the blood–brain barrier (BBB). Concurrently, nanotechnology offers groundbreaking tools, including nanoparticle-based drug delivery systems for blood–brain barrier (BBB) penetration, quantum dot biosensors for early Aβ detection, and CRISPR-nano platforms for APOE4 gene editing. We discuss how integrating these disciplines addresses critical challenges in AD management—from early biomarker detection to precision therapeutics—and outline future directions for translating these innovations into clinical practice. 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

Neurological damage, a debilitating condition closely associated with chronic neuroinflammation, currently lacks disease-modifying treatments, with management limited to symptomatic relief. Vitamins B6 (VB6), B12 (VB12), and proteolipid protein 1 (PLP-1) exhibit multimodal neuroprotective and anti-inflammatory effects; however, their therapeutic potential is limited by low bioavailability and inadequate ability to cross the blood–brain barrier (BBB). To address these limitations, we developed an ursolic acid-based nanoparticle system for the intranasal co-delivery of VB6, VB12, and recombinant PLP-1. The PLP-1 model predicted by AlphaFold3 was used for molecular docking. The docking results confirmed high-affinity binding interactions with VB6 and VB12, elucidating the mechanistic basis of their synergy. In vitro studies using a glucose-deprived PC12 cell injury model identified an optimal synergistic molar ratio of 10:1:2 (VB6: VB12: PLP-1). This combination significantly upregulated neuroprotective markers (PLP-1 and PGC-1α) and downregulated the pro-inflammatory cytokine TNF-α. In a mouse model of neural damage, the nano-encapsulated combination therapy demonstrated improved pharmacokinetics and significantly attenuated neuroinflammation and oxidative stress in brain tissue. This was evidenced by lower TNF-α and IL-1β levels and elevated GSH and SOD concentrations compared to free drug controls. The treatment regimen showed no detectable hepatorenal toxicity. Our findings demonstrate that this nanoformulation represents a safe, effective, and promising disease-modifying strategy to treat vestibular dysfunction by synergistically targeting its underlying neuroimmunological mechanisms. Full article

Background: This work aimed to enhance the solubility of Tadalafil (TDL), a BCS Class II drug, by preparing Type IV lipid-based formulations. Methods: Type IV formulations were prepared using surfactants and/or hydrophilic co-surfactants, resulting in oil-free systems. Results: Based on the solubility test, Transcutol^® HP exhibited the highest solubility for TDL (48.33 ± 0.004 mg/mL) and was selected as the co-surfactant. Among surfactants, Kolliphor^® PS80 (42.74 ± 2.29 mg/mL), Kolliphor^® EL (41.87 ± 2.50 mg/mL), Kollisolv^® PEG 400 (40.70 ± 0.30 mg/mL), and Kolliphor^® HS15 (31.40 ± 3.63 mg/mL) demonstrated high solubilization capacity. These were used to prepare formulations without the addition of an oil phase. The developed formulations resulted in a system with a nano-droplet size (<50 nm) and PDI values < 0.3, which was clear, transparent, and resistant to pH dilutions. The optimum Type IV lipid formulations were further characterized and demonstrated good thermodynamic stability under temperature and pH changes. The optimized formulation was adsorbed onto different carriers and transformed into solid TDL-loaded formulations. The in vitro dissolution rate of the drug from the solidified lipid formulations was studied in various dissolution media. It was observed that the solid formulations prepared with Neusilin US2^® (2:1) exhibited a significantly higher dissolution of over 95% within 5 min compared to the marketed product. The in vitro lipolysis studies demonstrated that F2 formulation maintained TDL in a supersaturated state throughout digestion, with limited enzymatic degradation of the excipients. Cytotoxicity evaluation using the MTT assay in Caco-2 cells confirmed the biocompatibility of both drug-free and TDL-loaded formulations, with IC₅₀ values of 19.55 µg/mL and 17.55 µg/mL, respectively. Conclusions: The overall results suggested that the developed solid Type IV lipid formulations can improve the dissolution rate of TDL, which would potentially lead to an improvement in its oral bioavailability and, consequently, a reduction in the treatment dose as a safe delivery system. Full article

The advent of nanotechnology has revolutionized the field of medicine, particularly in the development of targeted therapeutic strategies. Among these, radiolabeled nanomaterials have emerged as promising tools for both diagnostic and therapeutic applications, offering precise delivery of radiation to diseased tissues while minimizing damage to healthy ones. Notably, Lutetium-177 (¹⁷⁷Lu) has gained significant attention due to its favorable emission properties and availability that render it suitable for imaging and therapeutic purposes. When integrated with magnetic nano-formulations, ¹⁷⁷Lu-labeled systems combine the benefits of targeted radiation therapy (TRT) with the unique properties of magnetic nanoparticles (MNPs), such as magnetic resonance imaging (MRI) contrast enhancement and magnetically guided drug delivery to address challenges in diagnosis and treatment of diseases, such as cancer. By examining the latest advancements in their design, particularly surface functionalization and bioconjugation strategies, this study aims to highlight their efficacy in targeted therapy, imaging, and theranostic applications. Furthermore, we discuss the current challenges, such as scalability, biocompatibility, and regulatory hurdles, while proposing future directions to enhance their clinical translation. This comprehensive review underscores the transformative potential of ¹⁷⁷Lu-labeled magnetic nano-formulations in precision medicine and their role in shaping the future of therapeutic interventions. Full article

Andrographis paniculata, a medicinal plant widely found in Asia, contains andrographolide as its main active compound, known for its wide-ranging pharmacological effects, including anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic properties. Recent investigations have highlighted the anti-infective potential of andrographolide and its derivatives, with demonstrated antiviral, antibacterial, and antimalarial activities. This review summarizes progress in andrographolide’s anti-infective applications, focusing on its structure–activity relationship (SAR) and mechanisms of action. Researchers have used semi-synthetic methods, such as esterification, oxidation, Michael addition, salification, and hybrid design, to enhance andrographolide’s physicochemical properties and biological activity. These derivatives show potent antiviral activity against RNA and DNA viruses, antibacterial activity against Gram-positive and Gram-negative bacteria, antifungal effects, and antiparasitic activity against Plasmodium spp. and Leishmania spp. Nevertheless, poor solubility and limited bioavailability still hinder their clinical translation. Strategies such as nano delivery systems and β-cyclodextrin complexes are discussed to improve bioavailability. Although andrographolide itself has not received regulatory approval as a stand-alone drug, several andrographolide-containing preparations have been clinically used in certain countries. Overall, this review brings together evidence on antiviral, antibacterial, antifungal, and antiparasitic activities, linking them with structure–activity trends and pharmacokinetic insights, thereby providing a consolidated foundation for future development and clinical translation. Full article

Background/Objectives: A non-toxic nano-platform which can increase drug-loading rate and synergistically increase antitumor effect is very ideal. This study provides the concept that a combination of photothermal therapy with chemotherapy and anti-inflammatory therapy will be achieved by ablation of the local tumor, robust strategies for the suppression of distant tumors with enhanced antitumor therapy outcomes. Methods: In this study, the chemotherapeutic drug cisplatin (DDP) and the anti-inflammatory drug Aspirin-DL-Lysine (ADL) were loaded into a hollow porous nanomaterial zeolitic imidazolate framework-8 (ZIF-8), which was then coated with polydopamine, in order to form near-infrared absorption organic nanoparticles DDP-ADL@ZIF-8@PDA with excellent photothermal conversion efficiency. The antitumor efficacy of the nanodrug was evaluated through physicochemical characterization, cell biology studies, and animal experiments. Results: Photothermal therapy (PTT) of polydopamine combined with DDP and ADL can reduce inflammation and the immunosuppressive tumor microenvironment, and enhance antitumor effect. The results showed that the combined therapy could effectively eliminate the primary tumor, shrink the distant tumor, and inhibit the metastasis of the tumor. PTT in combination with chemotherapy and anti-inflammatory therapy can inhibit the expression of inflammatory factors, significantly reducing tumor immunosuppression by eliminating bone marrow-derived suppressor cells and increasing levels of cytotoxic T lymphocyte. Conclusions: This study successfully developed a DDP-ADL@ZIF-8@PDA nanomedicine for effective drug delivery, synergistic photothermal therapy, and anti-inflammatory attenuated immunotherapy to enhance treatment of human cervical cancer xenografts in mice. Overall, the combination of photothermal therapy with chemotherapy and anti-inflammatory therapy on a nano-platform has great potential for antitumor therapy applications. Full article

This study emphasizes overcoming the challenges of targeted drug delivery in colon cancer therapy by developing gastrointestinal (GI) stable, pectin-coated nanoliposomes for the oral delivery of Apigenin-Cyclodextrin Complex as an in situ gel formation. Initially, the formulation was strategically designed using design expert software for formulation optimization. FTIR and XRD studies were conducted to ensure physical compatibility and to confirm the encapsulation of apigenin within the formulation. In process optimization, among all seventeen formulations run tested, PNL (Api-Cy)-13 was identified for the highest drug loading, favourable size dimension of particle with zeta potential, and spherical external morphology through SEM analysis. The metered drug release during an in vitro study for PNL (Api-Cy)-13 was remarkably high (more than 75% of drug availability in the colonic environment, precisely in contrast to only 20% in the gastric phase in a sustained release manner), focused on colon drug targeting as an in situ gel. Furthermore, apigenin release from PNL (Api-Cy)-13 in an ex vivo chick ileum permeability study was observed both in the absence and presence of 1% vancomycin. An incremental apigenin release in the absence of the antibiotic (1% vancomycin) indicated gut microbial-associated and pectinase-mediated drug release. Here, pectin degradation materializes by the colonic microbial environment, which facilitates desirable incremental colonic drug permeation. Finally, an in vitro MTT assay and a competitive flowcytometric cell uptake study with PNL (Api-Cy)-13 using HCT-116 cells proved significant superiority in cytotoxicity profile for apigenin when delivered as an optimized coated nanoliposome in comparison to free apigenin or other non-modified nano-formulation. Also, the inhibition of the cell efflux process was validated by Multidrug Resistance 1 (MDR1) gene regulation. These observations establish an undoubted promise for the novel biopolymer, pectin-based apigenin-cyclodextrin nanoliposomes as targeted therapy in colon cancer with significant in vivo pharmacokinetics and safety profile. Full article

Silica aerogel has garnered significant attention in the biomedical field, primarily due to its unique combination of a three-dimensional structure, low density, tunable nanoscale pores, and an extensive surface area. These intrinsic properties render it as an exceptional candidate for advanced drug delivery systems (DDSs). In the realm of medical applications, silica aerogels have demonstrated remarkable potential, especially in nanoscale DDSs. Traditional drug delivery methods, such as capsules and tablets, are often plagued by several drawbacks, including poor bioavailability, lack of target specificity, and multidrug resistance. These limitations necessitate the development of more efficient and targeted drug delivery systems. Recent advancements in the synthesis and modification of silica aerogels have significantly enhanced their biocompatibility and functionalization capabilities. These improvements have further bolstered their potential for controlled release and targeted delivery of therapeutic agents. This study is based on silica aerogel-based nanocarrier systems, providing an in-depth exploration of its fundamental principles, preparation processes, and recent advancements. Based on this, we summarize the drug delivery methods, drug release characteristics, and diverse medical applications of silica aerogels. Additionally, we discuss the challenges and future prospects of applying silica aerogels in drug delivery systems, aiming to provide a comprehensive overview of this field. Full article

According to the World Health Organization, Alzheimer’s disease and other forms of dementia were the seventh leading cause of death in 2021. The prevalence of these disorders is predictable to increase with life expectancy, and their control is hampered by several factors, including late diagnosis due to the lack of specific biomarkers and the absence of disease-modifying treatments, as currently available therapies can only lighten some of the symptoms. Nanotechnology could be the key to overcoming some of the limitations associated with neurodegenerative diseases, as nanomaterials have excellent properties compared to their bulk counterparts and can be used as drug delivery systems, diagnostic tools and platforms for tissue regeneration. Chitosan is a biopolymer with numerous properties that impart it with great potential for biomedical applications, in particular its ability to cross the blood–brain barrier and its versatility in nanoscale design. In this context, the aim of this review is to provide an in-depth analysis of the latest developments and future opportunities for chitosan (nano)formulations for the treatment and management of neurodegenerative diseases. Full article