Search Results (3,415)

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive dilation and weakening of the abdominal aortic wall. Despite advances in surgical repair, rupture remains associated with mortality rates exceeding 65%, and no effective pharmacological therapy exists to prevent disease progression. Increasing evidence highlights chronic inflammation, extracellular matrix degradation, and immune dysregulation as central drivers of AAA pathogenesis. Among these mechanisms, the thrombospondin-1 (TSP1)–CD47 signaling axis has emerged as a critical upstream regulator of vascular inflammation. By engaging CD47, TSP1 promotes macrophage activation, impairs efferocytosis, and sustains a self-perpetuating inflammatory loop that accelerates tissue destruction. This positions the TSP1–CD47 pathway as more than a bystander in aneurysm biology, linking immune activation with structural failure of the aortic wall. The therapeutic relevance of this axis is underscored by the development of CD47-targeted agents in oncology, which restore phagocytosis and immune balance. Repurposing such strategies for vascular medicine, in combination with advanced drug delivery systems, offers a promising avenue for disease-modifying therapy in AAA. Notably, two targeted drug delivery approaches have been described: both employ bispecific targeting of CD47 in combination with a macrophage-specific marker, using immunotoxins encapsulated in liposomal carriers to enhance selectivity and therapeutic efficacy. By shifting focus from structural repair to immune modulation, targeting the TSP1–CD47 axis with these strategies has the potential to redefine the clinical management of this condition. Full article

Saffron (Crocus sativus L.) is one of the most valued spices worldwide, rich in bioactive apocarotenoids such as crocins, picrocrocin, and safranal, which display antioxidant, neuroprotective, and anticancer properties. Saffron’s chemical composition is critical for its therapeutic efficacy and a combination of components appears essential to reach the best protection and increase tissue resilience, so stigmas were subjected to hydroalcoholic extraction followed by purification via solid-phase extraction to enriched crocin and picrocrocin fractions. The extracts were included in liposomes to enhance their bioavailability and gastrointestinal absorption by oral administration while protecting them in the harsh gastric environment, increasing their permeation and sustaining their release in the gastrointestinal tract. Liposomes were prepared by the reverse-phase evaporation method using saturated or unsaturated lipids extracted from soy. Encapsulation efficiency was determined by HPLC monitoring of trans-4GG crocin, cis-4GG crocin, and picrocrocin. The results indicate that liposomes show greater encapsulation capacity for hydrophilic apocarotenoids such as crocins (≈90% for cis-4GG, ≈50% for trans-4GG crocin) with respect to picrocrocins (<20%). These findings support the application of liposomal carriers to improve the stability, shelf-life, and potential bioavailability of saffron’s bioactive properties for nutraceutical, pharmaceutical, and functional food applications. Full article

Background: Seasonal influenza vaccines must be reformulated annually due to the high genetic variability and antigenic drift of circulating influenza viruses. The annual update, guided by World Health Organization (WHO) recommendations, results in significant challenges, including compressed production time periods, elevated manufacturing costs, and global distribution pressures. Moreover, mismatches between vaccine strains and circulating viruses can severely reduce protective efficacy, underscoring the urgent need for broadly protective and long-lasting influenza vaccines. Methods: In this study, we developed an adjuvanted trivalent recombinant influenza virus-like particle vaccine (a-RIV) using the baculovirus–insect cell expression system and formulated it with an AS01-like adjuvant. The vaccine comprises full-length hemagglutinin (HA) proteins from WHO-recommended seasonal influenza strains: A/H1N1 (AH1), A/H3N2 (AH3), and B/Victoria (B/vic) lineages. The purified HA proteins were subsequently formulated with a liposomal adjuvant to enhance the immunogenicity. Results: In mouse immunization studies, the a-RIV vaccine elicited significantly stronger humoral and cellular immune responses than the licensed recombinant vaccine Flublok and the conventional inactivated influenza vaccine (IIV). High levels of functional anti-HA antibodies and antigen-specific T cell responses persisted for at least six months post-vaccination. Moreover, a-RIV induced broadly reactive antibodies capable of cross-binding to heterologous AH1 and AH3 influenza strains. Conclusions: Our data demonstrate that the a-RIV elicits enhanced, durable, and broadly cross-reactive immune responses against multiple influenza subtypes. These findings support the potential of adjuvanted recombinant HA-based vaccine as a promising candidate for the development of next-generation influenza vaccine. Full article

Red palm oil (RPO) is a rich source of bioactive compounds, including carotenoids, tocopherols, tocotrienols, and polyphenols, which contribute to its potent antioxidant and anti-inflammatory properties. This review summarizes the current understanding of RPO composition, bioactivity, and potential applications in health and cosmetics. Current preclinical and small-scale clinical studies suggest that RPO bioactives can mitigate oxidative stress, modulate inflammatory pathways, and improve skin barrier function. Strategies to enhance stability and bioavailability, such as microencapsulation and formulation into emulsions or liposomes, are also discussed. The manuscript highlights the potential of RPO as a natural functional ingredient in dietary, nutraceutical, and cosmetic products. Comprehensive evaluation of these bioactive compounds provides insights for future research and practical applications in promoting human health. Full article

Sertaconazole nitrate (SN), a broad-spectrum antifungal agent, is clinically employed against diverse dermatophyte infections. Its therapeutic efficacy, however, is constrained by poor aqueous solubility (0.006 mg/mL) and insufficient skin penetration from current commercial formulations. To address these limitations, this research focused on developing, optimizing (using a 3² factorial design), and assessing a topical nanovesicular gel incorporating sertaconazole nitrate-loaded ultraflexible liposomes (SN-UFLs) to enhance antifungal performance. The vesicles exhibited near-spherical morphology, with sizes ranging from 104.40 ± 1.20 to 151.90 ± 2.14 nm, zeta potential (ZP) values between −21.50 ± 1.25 and −51.20 ± 2.25 mV, and entrapment efficiency (EE) values from 77.60 ± 2.50% to 86.04 ± 3.20%. The optimized SN-UFL formulation (OPT-SN-UFL) was then integrated into a carbopol gel base. This SN-UFL-Gel was characterized for pH (6.5 ± 0.20), viscosity (499.66 ± 15 cP), spreadability (205 ± 1.50%), extrudability (154.18 ± 2.48 g/cm²), and drug content (96.7 ± 2.50%), as well as ex vivo skin permeation, skin irritation potential, and in vitro and in vivo antifungal efficacy. Compared with the marketed formulation, higher drug permeation and skin deposition were observed for SN-UFL-Gel. The SN-UFL-Gel exhibited a larger zone of inhibition (25 ± 1.50 mm) against Candida albicans compared to the commercially available formulation (20 ± 1.72 mm). The in vivo animal studies showed that SN-UFL-Gel showed better antifungal activity by efficient inhibition of infection induced in rats with Trichophyton mentagrophytes. The SN-UFL-Gel showed no signs of skin irritation and was stable at 4 ± 1, 25 ± 2, and 40 ± 2 °C for 3 months. Conclusively, the current work divulged successful augmentation of the overall effectiveness of sertaconazole nitrate by using deformable liposomes as a promising nanocarrier. Full article

The escalating threat of antibiotic resistance has prompted the search for alternative antibacterial therapies. Antibacterial photodynamic therapy (aPDT), which utilizes light-activated photosensitizers to generate reactive oxygen species (ROS), offers a promising, non-invasive approach. The aim of this review is to analyze recent advances in nanoparticle-mediated aPDT and synthesize crucial design principles necessary to overcome the current translational barriers, thereby establishing a roadmap for future clinically applicable antimicrobial treatments. Emerging nanoparticle platforms, including upconverting nanoparticles (UCNPs), carbon dots (CDs), mesoporous silica nanoparticles (MSNs), liposomes, and metal–organic frameworks (MOFs), have demonstrated improved photosensitizer delivery, enhanced ROS generation, biofilm disruption, and targeted bacterial eradication. Synergistic effects are observed when aPDT is integrated with photothermal, chemodynamic, or immunotherapeutic approaches. The review further examines the mechanisms of action, biocompatibility, and antibacterial performance of these nanoparticle systems, particularly against drug-resistant strains and in challenging environments such as chronic wounds. Overall, nanomaterial-mediated aPDT presents a highly promising and versatile solution to antimicrobial resistance. Future perspectives include the integration of artificial intelligence to personalize aPDT by predicting optimal light dosage and nanoplatform design based on patient-specific data, rigorous clinical validation through trials, and the development of safer, more efficient nanoparticle platforms. Full article

Tuberculosis (TB) remains a significant worldwide health challenge due to the limitations of conventional treatments and the rising incidence of drug-resistant Mycobacterium tuberculosis strains. This review consolidates the advancements in nanotechnology-based therapeutics, inhalable formulations, CRISPR–Cas tools, host-directed therapies (HDTs), and nanoparticle-based vaccine development aimed at enhancing TB management. Novel nanocarriers such as liposomes, solid-lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (NPs) offer enhanced bioavailability of drugs, sustained release, as well as targeted delivery to infected macrophages, thereby reducing systemic toxicity and dosing frequency. Inhalable nanomedicines provide localized delivery to the pulmonary site, enhancing the concentration of the drug at the primary site of infection. CRISPR–Cas technology is emerging as a transformative approach to disabling drug-resistant genes and enhancing diagnostic precision. HDTs, including agents like vitamin D and metformin, show potential in modulating host immune responses and enhancing pathogen clearance. Nanoparticle-based vaccines, including mRNA and antigen-conjugated platforms, aim to overcome the limitations of the BCG vaccine by enhancing antigen presentation and eliciting stronger, longer-lasting immunity. Collectively, these modalities mark a shift toward more personalized, effective, and less toxic TB therapies. However, challenges such as regulatory approval, safety, scalability, and accessibility remain. This review highlights the integrated potential of nanomedicine, gene editing, and immunomodulation to transform TB care and combat drug resistance, paving the way for more robust and durable treatment strategies. Full article

Vitamin C, a water-soluble micronutrient, is one of the most widely used dietary supplements pertaining to its vital role in maintaining overall human health, particularly through its potent antioxidant and immune-supportive functions. This mini review summarizes key pharmacokinetic constraints of vitamin C and evaluates formulation strategies aimed at improving its systemic availability. Achieving sustained optimal plasma levels of vitamin C remains challenging due to its dose-dependent absorption, tissue saturation, rapid renal clearance, and short half-life. These pharmacokinetic limitations restrict systemic retention, with high oral doses providing only marginal increases in plasma concentrations and necessitating multiple daily administrations. Conventional vitamin C supplements show efficient absorption only at low to moderate doses, while higher intakes are restricted by transporter saturation and increased renal excretion. Alternative delivery systems such as liposomal encapsulation, esterified derivatives, nano-emulsions, and co-formulations with bioenhancers have been examined; however, evidence for prolonged systemic retention remains inconsistent. The sustained-release formulation of vitamin C shows more reliable outcomes, demonstrating prolonged plasma exposure, higher steady-state concentrations, and potential for improved compliance through reduced dosing frequency. While further robust comparative studies are needed, current evidence suggest that advanced formulation approaches, particularly sustained-release delivery, may help overcome these pharmacokinetic limitations, thereby supporting improved clinical utility of vitamin C supplementation. Full article

Lyophilization (freeze-drying) has become a cornerstone pharmaceutical technology for stabilizing biopharmaceuticals, overcoming the inherent instability of biologics, vaccines, and complex drug formulations in aqueous environments. The appropriate literature for this review was identified through a structured search of several databases (such as PubMed, Scopus) covering publications from late 1990s till date, with inclusion limited to peer-reviewed studies on lyophilization processes, formulation development, and process analytical technologies. This succinct review examines both fundamental principles and cutting-edge advancements in lyophilization technology, with particular emphasis on Quality by Design (QbD) frameworks for optimizing formulation development and manufacturing processes. The work systematically analyzes the critical three-stage lyophilization cycle—freezing, primary drying, and secondary drying—while detailing how key parameters (shelf temperature, chamber pressure, annealing) influence critical quality attributes (CQAs) including cake morphology, residual moisture content, and reconstitution behavior. Special attention is given to formulation strategies employing synthetic surfactants, cryoprotectants, and stabilizers for complex delivery systems such as liposomes, nanoparticles, and biologics. The review highlights transformative technological innovations, including artificial intelligence (AI)-driven cycle optimization, digital twin simulations, and automated visual inspection systems, which are revolutionizing process control and quality assurance. Practical case studies demonstrate successful applications across diverse therapeutic categories, from small molecules to monoclonal antibodies and vaccines, showcasing improved stability profiles and manufacturing efficiency. Finally, the discussion addresses current regulatory expectations (FDA/ICH) and compliance considerations, particularly regarding cGMP implementation and the evolving landscape of AI/ML (machine learning) validation in pharmaceutical manufacturing. By integrating QbD-driven process design with AI-enabled modeling, process analytical technology (PAT) implementation, and regulatory alignment, this review provides both a strategic roadmap and practical insights for advancing lyophilized drug product development to meet contemporary challenges in biopharmaceutical stabilization and global distribution. Despite several publications addressing individual aspects of lyophilization, there is currently no comprehensive synthesis that integrates formulation science, QbD principles, and emerging digital technologies such as AI/ML and digital twins within a unified framework for process optimization. Future work should integrate advanced technologies, AI/ML standardization, and global access initiatives within a QbD framework to enable next-generation lyophilized products with improved stability and patient focus. Full article

Ischemic stroke remains a major cause of mortality and long-term disability, yet current therapeutic strategies are largely limited to reperfusion approaches such as intravenous thrombolysis and thrombectomy, which are constrained by narrow treatment windows and the risk of complications. Moreover, the blood–brain barrier (BBB) severely restricts drug penetration into the injured brain, limiting the translation of promising neuroprotective agents into clinical success. Intranasal (IN) delivery has emerged as a compelling alternative route that bypasses the BBB and enables rapid access to the central nervous system through olfactory, trigeminal, and perivascular pathways. This narrative review highlights recent advances in preclinical research on IN therapeutics for ischemic stroke, ranging from small molecules and biologics to nucleic acids and cell-based therapies. Particular emphasis is placed on the application of nanotechnology, including extracellular vesicles, liposomes, and inorganic nanoparticles, which enhance drug stability, targeting, and bioavailability. Studies demonstrate that IN delivery of growth factors, cytokines, and engineered stem cells can promote neurogenesis, angiogenesis, white matter repair, and functional recovery, while nanocarriers further expand the therapeutic potential. Overall, intranasal delivery represents a promising and non-invasive strategy to overcome the limitations of conventional stroke therapies, offering new avenues for neuroprotection and regeneration that warrant further investigation toward clinical translation. Full article

Liposomes modified with slightly acidic pH-sensitive peptides (SAPSp-lipo) are effectively delivered to tumor tissues, followed by cellular uptake in the tumor microenvironment. Although SAPSp-lipo can penetrate tumor tissues via the interspace route between cancer cells and the extracellular matrix (ECM), penetration needs to be enhanced to deliver liposomes into tumor cores comprising malignant cancer cells. To enhance the intratumoral penetration of SAPSp-lipo, we focused on the internalizing RGD peptide (iRGD), which can penetrate tumor tissue, differing from the penetration mechanism of SAPSp. In this study, we developed liposomes modified with iRGD-conjugated SAPSp (SAPSp-iRGD-lipo). Compared with SAPSp-lipo, SAPSp-iRGD-lipo was delivered to deeper regions within both spheroids and tumor tissues. The enhanced penetration was suppressed by a co-treatment with a Neuropilin-1 inhibitor, and the fluorescence signals from intratumorally injected SAPSp-iRGD-lipo were localized in Neuropilin-1-expressing regions, indicating a Neuropilin-1-mediated tumor penetration. Moreover, SAPSp-iRGD-lipo reduced F-actin formation in monolayered cells and was not localized in F-actin-rich regions in tumors, suggesting that SAPSp-iRGD-lipo facilitates tumor penetration through actin depolymerization. In addition, anticancer siRNA delivered by SAPSp-iRGD-lipid nanoparticles effectively induced apoptosis in cells under slightly acidic conditions. Taken together, SAPSp-iRGD-modified nanoparticles represent a novel class of tumor-penetrable and microenvironment-responsive drug carriers capable of efficient intratumoral delivery and therapeutic activity. Full article

Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC_0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák’s post hoc multiple-comparisons test and the Mann–Whitney test (α = 0.05). Results: The AUC_0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 ± 661.5 vs. 1929.8 ± 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 ± 7.3% vs. 2.0 ± 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol. Full article

Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article

L-asparaginase (L-ASNase) is a vital enzymatic drug widely used for treating acute lymphoblastic leukemia (ALL) and certain lymphomas. However, its clinical application is often limited by a short plasma half-life, pronounced immunogenicity, and systemic toxicities. To address these challenges, we recently developed conjugates of L-ASNase with cationic polymers, enhancing its cytostatic activity by increasing enzyme binding with cancer cells. The present study focuses on the development of liposomal formulations of E. coli L-asparaginase (EcA) and its conjugates with cationic polymers: the natural oligoamine spermine (spm) and a synthetic polyethylenimine–polyethyleneglycol (PEI-PEG) copolymer. This approach aims to improve enzyme encapsulation efficiency and stability within liposomes. Various formulations—including EcA conjugates with polycations incorporated into 100 nm and 400 nm phosphatidylcholine/cardiolipin (PC/CL, 80/20) anionic liposomes—were synthesized as a delivery system of high enzyme load. Fourier Transform Infrared (FTIR) spectroscopy confirmed successful enzyme association with liposomal carriers by identifying characteristic changes in the vibrational bands corresponding to both protein and lipid components. In vitro release studies demonstrated that encapsulating EcA formulations in liposomes more than doubled their half-release time (T_1/2), depending on the formulation. Cytotoxicity assays against Raji lymphoma cells revealed that liposomal formulations, particularly 100 nm EcA-spm liposomes, exhibited markedly superior anti-proliferative activity, reducing cell viability to 4.5%, compared to 35% for free EcA. Confocal Laser Scanning Microscopy (CLSM) provided clear visual and quantitative evidence that enhanced cellular internalization of the enzyme correlates directly with its cytostatic efficacy. Notably, formulations showing higher intracellular uptake produced greater cytotoxic effects, emphasizing that hydrolysis of asparagine inside cancer cells, rather than extracellularly, is critical for therapeutic success. Among all tested formulations, the EcA-spermine liposomal conjugate demonstrated the highest fluorescence intensity within cells providing enhanced cytotoxicity. These results strongly indicate that encapsulating cationically modified L-ASNase in liposomes is a highly promising strategy to improve targeted cellular delivery and prolonged enzymatic activity. This strategy holds significant potential for developing more effective and safer antileukemic therapies. Full article

Antimicrobial resistance (AMR) is one of the most critical challenges to global public health in the 21st century, posing a significant threat to healthcare systems and human health due to treatment failure and high mortality. The World Health Organization (WHO) estimates that, without effective interventions, AMR-associated infections could cause 10 million deaths annually and economic losses of up to 100 trillion US dollars by 2050. The rapid spread of drug-resistant strains, especially in hospital and community settings, has significantly reduced the efficacy of traditional antibiotics. With the continuous advancements in relevant research, bacteriophage (Phage) therapy is constantly innovating in the antimicrobial field. The application of frontier technologies, such as phage cocktails and engineered phages, has significantly enhanced the broad spectrum and high efficiency of phage therapy, which is gradually becoming a new generation of tools to replace antibiotics and effectively combat pathogenic bacteria. However, phage therapy is facing several challenges, including phage inactivation by gastric acid, enzymes, ultraviolet light, and mechanical stress, as well as the potential risk of bacterial phage resistance. Advanced encapsulation technologies such as electrospun fibers, liposomes, chitosan nanoparticles, and electrospray provide solutions to these problems by protecting phage activity and enabling controlled release and targeted delivery. This review addresses phage therapeutic studies of Salmonella, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes, summarizes the recent advances in phage research, and details the current development and applications of encapsulated phage technologies across various delivery modes. Full article