Search Results (441)

Nanomedicine has yielded clinically useful platforms, including liposomes, albumin-bound nanoparticles, and lipid nanoparticles; yet, many systems translate poorly because of nonspecific biodistribution, limited target-site accumulation, inefficient cellular uptake and intracellular delivery, immune clearance, and off-target toxicity. These bottlenecks are often shaped at cell membrane interfaces, where therapeutic materials are recognized, retained, internalized, or cleared and may elicit unsafe responses. Here, we frame cell membrane biophysics as a therapeutic interface for nanomedicine. We examine how lipid organization and fluidity, mechanics, electrochemical state, glycocalyx architecture, and membrane protein identity shape recognition, adhesion, endocytosis, fusion, trafficking, immune responses, and drug release. We assess how disease-associated membrane remodeling can create candidate therapeutic entry points and delivery barriers across cancer, neurodegeneration, inflammation, infection, and vascular disease. We then analyze receptor-mediated targeting, lipid-domain-associated uptake, membrane-coated nanocarriers, engineered extracellular vesicles, and hybrid platforms, with explicit context-of-use definitions and design boundaries. Finally, we propose translational qualification through function-linked critical quality attributes, mechanism-relevant potency assays, context-matched models, in vivo pharmacology and immune safety, scalable manufacturing, and regulatory evaluation. Progress will depend less on descriptive membrane mimicry than on measurable, reproducible, and qualified membrane-dependent functions. Full article

Acute and chronic inflammation underlies the pathogenesis of numerous diseases, including autoimmune disorders, atherosclerosis, infections, and cancer. Although non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are widely used to control inflammation, their clinical utility is limited by adverse effects such as gastrointestinal toxicity and immunosuppression. Specialized pro-resolving mediators (SPMs), a family of endogenous lipid mediators derived from omega-3 fatty acids, have emerged as promising therapeutics because they actively promote the resolution of inflammation without suppressing host immunity. However, their clinical translation is hindered by poor chemical stability, rapid metabolic degradation, and short circulation half-lives. To overcome these limitations, a variety of delivery platforms—including liposomes, extracellular vesicles, PLGA nanoparticles, and hydrogels—have been developed to improve SPM stability, pharmacokinetics, and therapeutic efficacy. This review summarizes the cellular targets of SPMs, current delivery challenges, and emerging strategies for cell- and tissue-specific SPM delivery. We also discuss future opportunities for targeted SPM therapies in the treatment of inflammatory diseases and cancer. Full article

Background/Objectives: Olive leaf polyphenols exhibit strong antioxidant and antidiabetic potential. However, their application in nutraceutical and pharmaceutical products is hindered by limited stability, poor solubility, and susceptibility to gastrointestinal degradation. Liposomes offer a viable strategy to enhance their protection and functional performance. Methods: A formulation-driven strategy was employed to develop a gastro-resistant liposomal system for olive leaf polyphenols. Extraction conditions were optimized using a Box–Behnken response surface design to maximize phenolic recovery while ensuring compatibility with phospholipid-based systems. Antioxidant activity and key secoiridoids were assessed by spectrophotometric assays and LC–MS/MS. The optimized extract was incorporated into uncoated and Eudragit^® L100-coated liposomes, which were physicochemically characterized. Antidiabetic effects were evaluated in intestinal STC-1 cells under glucose-induced hyperglycemic conditions. Results: The optimized extract (OE) exhibited high antioxidant activity (124.56 ± 9.57 mg GAE/g, 151.61 ± 2.77 mg TE/g, and 472.92 ± 26.14 mg TE/g in TPC, DPPH and FRAP assays, respectively). LC-HRMS metabolomic profiling confirmed a balanced phytochemical composition, with oleuropein as the main compound (143.144 ± 4.914 mg/g). The optimized Eudragit^®-coated liposomes were spherical unilamellar vesicles with a mean diameter of 101 ± 6.1 nm, moderate polydispersity (0.46 ± 0.02), and a negative zeta potential (−17 ± 3.5 mV). High entrapment efficiency was achieved, reaching 65 ± 2.1% for oleuropein and 96 ± 0.3% for hydroxytyrosol. The structural integrity of the vesicles was maintained during storage and in the simulated gastrointestinal environment. The nanoformulation reduced intestinal glucose uptake and intracellular reactive oxygen species levels, and restored GLP-1 levels. Conclusions: The combination of optimized extraction and liposome-based formulation enabled the development of stable, delivery-ready olive leaf polyphenols for potential nutraceutical and pharmaceutical applications. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs), including naproxen, are widely used for the treatment of pain and inflammation; however, their therapeutic application is limited by poor aqueous solubility and low bioavailability. This study aimed to synthesize and characterize a novel amino acid-based naproxen derivative, L-phenylalanine menthol ester naproxenate ([PheOMent][NAP]), develop liposomal formulations containing the obtained compound, and evaluate their physicochemical properties and transdermal delivery potential. The derivative was synthesized via a three-step procedure and characterized using NMR, FT-IR, TG, DSC, and XRD analyses. Compared with naproxen, [PheOMent][NAP] exhibited lower lipophilicity (log P = 1.36 vs. 1.70). Liposomal formulations containing the modified derivative showed high encapsulation efficiency (89.6–90.7%), higher than that observed for naproxen-loaded liposomes (51.7–54.7%). The prepared systems exhibited bimodal particle size distributions, comprising both submicrometre and micrometre vesicle populations depending on the preparation method, as well as negative zeta potential values (−18.17 to −23.72 mV) and pH values ranging from 6.18 to 7.07, demonstrating physicochemical characteristics suitable for topical formulations. In vitro permeation studies using porcine skin demonstrated markedly enhanced transdermal delivery of [PheOMent][NAP]. After 24 h, cumulative permeation exceeded that of naproxen formulations by more than 1.5-fold (416.7 vs. 281.6 μg cm⁻²). These findings indicate that liposomal formulations containing amino acid-modified naproxen derivatives represent a promising strategy for improving transdermal NSAID delivery. Full article

Xanthohumol (XN), a prenylated chalcone isolated from Humulus lupulus L., exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, and chemopreventive effects. However, its therapeutic application is limited by poor aqueous solubility, low chemical stability, and rapid clearance from the systemic circulation. The present study aimed to develop and characterize a novel nano-sized drug-delivery system for XN that combines favourable colloidal stability, efficient encapsulation, sustained release, and reduced recognition by macrophages (“stealth-like” properties). To achieve this, XN-loaded cationic liposomes were coated with two marine polysaccharides, iota-carrageenan (CAR) and fucoidan (FUC), followed by Ca²⁺-mediated cross-linking. Liposomes were prepared by the ethanol injection method, and formulation parameters were optimized using a 2³ + 1 full factorial design. Surface modification and cross-linking conditions were further optimized through polyelectrolyte titration and a Taguchi L9 orthogonal array. The resulting nanocarriers were evaluated for particle size, polydispersity, ζ-potential, encapsulation efficiency, release behavior, and cellular uptake. Both coatings significantly prolonged XN release compared with uncoated liposomes, with CAR-coated vesicles providing the most sustained release (≈55% over 48 h). In RAW264.7 macrophages, 50 µg/mL CAR-coated liposomes reduced cellular uptake by approximately 74% following 1-h incubation relative to uncoated controls and maintained this reduction over 2 h whereas FUC-coated vesicles afforded only transient early evasion. The cross-linked iota-carrageenan coating thus represents a promising strategy for conferring stable “stealth-like” characteristics to XN-loaded liposomes intended for prolonged drug delivery. Full article

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

Background/objectives: Foodborne diseases remain a significant global public health concern, requiring innovative and effective antimicrobial strategies to control food pathogens. Encapsulation of natural antimicrobials have attracted increasing interest. In this study, liposomes encapsulating pink pepper essential oil (PPEO), nisin, or their combination were developed, aiming to potentiate antimicrobial performance against foodborne pathogens. Methods: Phosphatidylcholine liposomes were prepared by the thin-film method and characterized by DLS and FTIR. The antimicrobial activity of nisin, PPEO, and liposomes was investigated by the agar diffusion method against foodborne pathogens like Staphylococcus aureus, Listeria monocytogenes, and Salmonella Typhimurium. Results: The liposomes exhibited nanometric size ranging from 91 to 107 nm, low polydispersity, and zeta potential between −3.73 and −7.39 mV, indicating well-defined vesicles with negative surface charges. Encapsulation enhanced antimicrobial efficacy, with nisin–PPEO liposomes stored for 21 days under refrigeration showing a sustained inhibition of L. monocytogenes, outperforming liposomes containing nisin alone. The combined antimicrobials also inhibited Gram-positive bacteria in milk agar, used as a simulated food system. Additionally, the antioxidant activity of PPEO was preserved upon encapsulation, especially under refrigeration, reinforcing the protective role of the liposomes. Conclusions: The co-encapsulation approach strengthened the stability and bioactivity of natural antimicrobials, highlighting liposomal delivery as a promising strategy to control foodborne bacteria. Full article

Extracellular vesicles (EVs) and liposomes are nanoscale drug delivery systems extensively investigated in oncology for their ability to improve pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents. Liposomes are clinically validated synthetic nanocarriers characterized by high versatility, scalable production, and established regulatory approval; however, their performance is limited by tumor heterogeneity, vascular barriers, adverse effects and inefficient intracellular drug release. EVs are naturally derived nanoparticles involved in intercellular communication and exhibit intrinsic biocompatibility, low immunogenicity, and biological targeting potential; yet their translation is constrained by heterogeneity, limited loading capacity, and manufacturing challenges. Different studies indicate complementary advantages between both systems, with EVs favoring biological targeting and immune modulation and liposomes enabling controlled formulation and pharmacokinetic optimization. These features have driven the development of hybrid EV–liposome nanovesicles, which integrate synthetic and biological properties to enhance tumor targeting, therapeutic efficacy, and payload diversity, including drugs, nucleic acids, and gene-editing systems. Despite promising preclinical results, challenges remain in scalability, standardization, and mechanistic understanding of in vivo behaviour. Overall, these hybrid strategies represent a promising platform for next-generation precision nanomedicine in cancer therapy and for advancing clinical translation by addressing key limitations of current delivery systems and improving therapeutic index and patient outcomes. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited actionable targets, early recurrence, metastatic propensity, and variable responses to immune checkpoint blockade. Therapeutic resistance is closely associated with myeloid immunosuppression, in which tumor-associated macrophages (TAMs) promote T-cell exclusion, stromal remodeling, angiogenesis, metabolic dysfunction, and resistance to cytotoxic and immune-based therapies. Anthraquinone compounds, including emodin, aloe-emodin, rhein, and chrysophanol, may support TAM reprogramming by regulating tumor-cell stress responses, endoplasmic reticulum stress, immunogenic cell death-associated signaling, redox balance, immunometabolism, and STAT3/NF-κB-related inflammatory pathways. However, poor aqueous solubility, heterogeneous biodistribution, unstable systemic exposure, and potential off-target toxicity limit their translational development. Liposomal delivery offers a formulation strategy to improve solubilization, biodistribution, TAM-associated uptake/engagement, intracellular release, and therapeutic exposure windows. This review discusses anthraquinone-loaded liposomes for TAM reprogramming in TNBC by integrating mechanistic rationale, evidence boundaries, delivery logic, formulation determinants, and translational challenges, with particular attention to stress chaperone proteins, lipid composition, vesicle lamellarity, membrane phase state, responsive release, clinically relevant liposomal formulations, and clinical developability. Overall, anthraquinone-loaded liposomes are better positioned as immune microenvironment recalibration platforms or synergistic modulators in combination therapy rather than as standalone cytotoxic agents for TNBC. Full article

Celastrol, one of the top five traditional natural products with high potential for modern drug development, exerts potent broad-spectrum biological activities, yet its poor aqueous solubility, low bioavailability, potential toxicity, and limited selectivity severely compromise its drug-likeness. Advanced drug delivery strategies, mainly including multifunctional polymer/lipid/protein-based organic nanoparticles, metal/silica-based inorganic nanoparticles, vesicles represented by liposomes, and nanoemulsions, are expected to overcome these druggability hurdles of celastrol via oral, transdermal or intravenous administration. This review summarizes recent progress in a series of celastrol formulations, including novel dosage forms and delivery routes accompanied with consequential pharmacological effects and mechanisms of action, which have the potential to bring about better druggability conducive to future medical treatment. Full article

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Exosomes are small vesicles released by cells that have attracted growing interest as drug delivery vehicles, particularly for brain diseases, where getting therapeutics across the BBB remains a fundamental problem. While conventional platforms such as liposomes, polymeric nanoparticles, and viral vectors often suffer from immune clearance and poor brain accumulation, engineered exosomes leverage natural cellular transport mechanisms to cross the BBB, protect cargo from degradation, and enable biocompatible interactions with target cells. This review takes a mechanistic and translational look at how exosomes are being engineered for CNS disorders, with a particular focus on glioblastoma. We cover exosome biogenesis through ESCRT-dependent and ESCRT-independent pathways, and how the competition between Rab27-driven secretion and Rab7-driven lysosomal degradation determines how many exosomes a cell releases, which has direct consequences for therapeutic production. We then discuss cargo loading strategies, from genetic approaches where donor cells are engineered to package specific molecules during biogenesis to physical methods like electroporation and sonication applied to isolated vesicles, alongside surface modification techniques for directing exosomes toward specific cell types. In glioblastoma, engineered exosomes have shown real promise for delivering chemotherapeutics across the BBB, targeting glioma stem cells, enabling CRISPR-based gene editing, and functioning as combined treatment and imaging tools. Applications in stroke and neurodegenerative diseases, where engineered exosomes carrying microRNAs and neuroprotective cargo have produced encouraging preclinical results, are also discussed. Scalable manufacturing and consistent targeting remain the hardest unsolved problems, and we outline emerging approaches including bioreactor-based production, programmable cargo loading, and patient-specific exosome design that are beginning to address these gaps. Overall, the progress reviewed here suggests that engineered exosomes are moving from an interesting biological concept toward a practically viable platform for CNS drug delivery. Full article

Background/Objectives: Intracellular delivery of RNA molecules is challenging. To solve this problem, many carrier systems are available, which are based on liposomes or polymers. Cyclodextrins are widely used excipients to increase the solubility of small molecules, but their polymer derivatives are able to deliver macromolecules. In the present study, we aimed to investigate and compare the siRNA and mRNA carrying capacity of a cationic quaternary ammonium β-cyclodextrin polymer (QABCDPS) and polyethylenimine (PEI). Methods: Cytotoxicity of the polymers was tested by the MTT method. Polyplexes were formulated with different nitrogen/phosphate ratios (NP), and their physicochemical properties were examined using dynamic light scattering and zeta potential measurements. Cellular internalization and intracellular effects of the polyplexes were investigated by confocal microscopy and flow cytometry. Results: QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns. Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers. Conclusions: In summary, QABCDPS is a low-toxicity carrier that shows some promise for mRNA delivery but is ineffective for siRNA silencing under the tested conditions and requires further structural optimization. Full article

Background: Increasing antifungal resistance, poor mucosal retention, and systemic side effects limit the effectiveness of currently available drugs. This study explores a novel topical nanotherapeutic approach for the targeted treatment of vulvovaginal candidiasis (VVC), employing green-synthesized silver nanoparticles (AgNPs) derived from Ascophyllum nodosum (AN) and incorporating ibrexafungerp citrate (IBC) into a liposomal formulation. Methods: AgNPs were biosynthesized using AN extract and characterized. Liposomes were prepared by thin-film hydration, and optimised using Central Composite design and characterized and optimized. Optimised liposomes, co-loaded with IBC and AN-AgNPs, were incorporated into a Carbopol-CMC-based topical gel. Results: FTIR shifts in the –OH (3332.31 cm⁻¹) and carbonyl (1636.87 cm⁻¹) bands with reduced intensity confirmed their involvement in Ag⁺ reduction and nanoparticle surface coordination, while the persistence of the 1015 cm⁻¹ band indicated the role of polysaccharides in capping and stabilizing the AN-AgNP. Characterization of the optimized liposomes (IBCL-11) revealed a particle size of 127.2 nm, a zeta potential of −43.8 mV, and a polydispersity index (PDI) of 0.35. Transmission Electron Microscopy (TEM) confirmed the presence of intact, spherical vesicles, while Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) validated the molecular dispersion and amorphous characteristics of the films. In vitro evaluations of the IBC liposomal gel demonstrated a sustained drug release of 72.6% over 24 h, alongside enhanced drug penetration across all skin layers. Antifungal assays highlighted the formulation’s potent efficacy, yielding Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values below 1 µg/mL. Furthermore, the treatments exhibited strong anti-biofilm properties; at MIC and MBC levels, AN-AgNPs achieved biofilm reductions of 45.27 ± 3.16% and 27.62 ± 2.13%, respectively, whereas IBCL-11 produced reductions of 34.25 ± 2.43% and 16.28 ± 1.72%. Conclusion: Ultimately, this study successfully developed an eco-friendly liposomal formulation co-loaded with AN-AgNPs and IBC, offering a promising and targeted therapeutic approach for the treatment of vulvovaginal candidiasis. Full article

Pulmonary fibrosis (PF) is a progressive and often fatal interstitial lung disease for which the currently available pharmacological therapies remain largely limited to slowing disease progression rather than reversing established fibrosis. This limitation has stimulated increasing interest in innovative therapeutic platforms capable of modulating complex fibrotic pathways. In this context, exosomes—nanoscale extracellular vesicles—have emerged as promising cell-free nanocarriers due to their intrinsic biocompatibility, low immunogenicity, and ability to be engineered for targeted drug delivery. In this review, we provide a comprehensive overview of both natural and engineered exosome-based strategies for the diagnosis and treatment of pulmonary fibrosis. We summarize recent advances in exosome engineering, including ligand functionalization, glycoengineering, and therapeutic cargo loading, highlighting how these approaches may support the development of more targeted and potentially personalized nanotherapeutic strategies. We further discuss emerging hybrid delivery platforms, such as exosome–liposome chimeras and hydrogel-based depots, which may enhance pulmonary retention, improve therapeutic durability, and enable controlled drug release. Finally, we outline key challenges and opportunities for clinical translation, including large-scale manufacturing, regulatory considerations, and clinically relevant delivery routes such as inhalation-based administration. Collectively, this review provides a translational perspective on engineered exosomes as emerging nanotherapeutic platforms for pulmonary fibrosis. Full article