Search Results (259)

Quercetin’s therapeutic potential is limited by its poor water solubility and rapid degradation. Natural clay minerals such as kaolinite present sustainable platforms for drug delivery, yet the molecular mechanisms of drug encapsulation are not fully understood. Specifically, the role of kaolinite’s structural polarity, its hydrophilic aluminol (001) and hydrophobic siloxane (00-1) basal surfaces, in selective drug adsorption remains unexplored. This study combines Monte Carlo sampling and Density Functional Theory (DFT) to provide the first quantitative, atomistic comparison of quercetin adsorption on both kaolinite surfaces. The results demonstrate a pronounced polarity-driven selectivity. Strong, exothermic adsorption (−206.65 kJ mol⁻¹) occurs on the hydrophilic (001) surface, stabilized by a network of five hydrogen bonds. In contrast, the hydrophobic (00-1) surface exhibits significantly weaker sorption (−147.16 kJ mol⁻¹), dominated by van der Waals interactions. Charge-transfer analysis shows that the hydrophilic (001) surface exhibits a net charge transfer of −0.198 e, approximately 2.4 times greater than that of the hydrophobic (00-1) surface (−0.083 e), consistent with differential electron density maps and partial density of states. By linking hydrogen bonding and charge transfer to adsorption energy, these results elucidate how surface polarity dictates drug encapsulation. This work establishes a predictive framework for designing kaolinite-based nanocarriers with optimized stability, bioavailability, and controlled release, guiding the development of sustainable drug delivery systems. It is noted that this DFT study models adsorption at 0 K using periodic slab models in a vacuum. Full article

Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by ¹H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H₂O₂. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against S. aureus. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering. Full article

Liposomes started to be studied for drug delivery in 1970s, taking advantage of their ability to encapsulate hydrophilic and hydrophobic drugs using biodegradable and biocompatible molecules. Nowadays, they remain one of the most promising strategies for drug delivery not only in cancer treatment but also in gene therapies and vaccines. The design and development of liposomal systems have evolved significantly over the past decades, moving from conventional formulations to advanced, stimulus-responsive, and multifunctional nanocarriers. Analogous to the myth of the Trojan Horse, liposomes must mislead the host immune system to reach the interior of cancer cells in order to deliver the therapeutic payload. There are many barriers that liposomes have to overcome to circulate through the bloodstream and specifically target cancer cells without damaging other tissues. Crucial parameters such as lipid composition, particle size, zeta potential, and PEGylation have been systematically optimized to enhance pharmacokinetics and biodistribution and to improve delivery efficiency. Furthermore, conjugation with antibodies, peptides, or small molecules has enabled active targeting, while stimuli such as pH, temperature, and enzymatic activity have been exploited for controlled drug release within the tumor microenvironment. Such innovations have laid the groundwork for translating liposomal formulations from the bench to clinical applications. In this paper, we evaluate the physicochemical features of liposomal design that underpin their suitability and efficacy for anticancer drug delivery. We aimed to focus on two main aspects: conducting an exhaustive review of the physicochemical parameters of liposomal drugs that have already been approved by regulatory agencies, while maintaining a pedagogical approach when explaining the key design parameters for the optimal design of liposomes in oncology in detail. Full article

Background/Objectives: PlantCrystals (PCs) are submicron particles derived from plants or parts of plants that can be produced by bead milling and/or high-pressure homogenization. Previous studies suggested improved dermal drug delivery of lipophilic active ingredients (API), which was explained by the formation of extracellular vesicles (EVs) during the production of PCs. The aim of this study was to investigate the suitability of PCs for enhancing the dermal penetration efficacy of different types of APIs. Methods: For this purpose, hydrophilic, lipophilic, and poorly water-soluble API-surrogates were loaded into PCs, and the dermal penetration efficacy, as well as the skin hydrating properties, were determined with an ex vivo porcine ear model. The penetration efficacy of the API surrogates from the PCs was compared to other formulation principles, e.g., simple API solutions, API loaded into classical EVs, and API added to the PCs after preparation. Silymarin-PCs—unloaded and loaded with API—were obtained by milling milk thistle seeds using small-scale bead milling. The PCs were characterized by size, size distribution, and zeta potential. Results: Milling of milk thistle seeds resulted in the formation of submicron particles with sizes of about 300 nm. Loaded PCs had a slightly larger size. Loading API into PCs resulted in improved dermal penetration when compared to the other formulation principles. The effect was most pronounced for the lipophilic API-surrogate (+90%, p < 0.001) and least pronounced for the hydrophilic API-surrogate (+2%, p > 0.05). The improved penetration of API from PCs can be explained by the formation of EVs during the production of the PCs in which the API is encapsulated. The encapsulation seemed to be highly efficient for the lipophilic API-surrogate, moderate for the poorly soluble API-surrogate, and very limited for the hydrophilic API-surrogate. All formulations increased the skin hydration significantly by about 30–40%. Conclusions: Milk thistle seeds are suitable for the production of PCs. These PCs improve skin hydration and enhance the dermal penetration of poorly water soluble and lipophilic APIs. However, they have limited effects on the dermal penetration efficacy of hydrophilic APIs. Full article

Implantable drug delivery devices may enhance therapeutic efficacy by allowing localized drug release, and they may overcome the drawbacks of conventional systemic treatment. Electrospun nanofibers are promising drug delivery systems due to their high surface-to-volume ratio, porosity, and easy drug encapsulation. However, controlled and sustained drug release is required to improve therapeutic efficacy and reduce toxicity. Also, the ability to tailor the release drug dose would be a useful tool for providing an optimal and individualized approach for the treatment. Therefore, the aim of the study was to analyze the possibility to tailor the release of paclitaxel (PTX) from poly(D,L-lactide-co-glycolide) (PDLGA) electrospun nonwovens by modifying the comonomer molar ratio. For this purpose, three kinds of polymers were compared with lactidyl-to-glycolidyl comonomer ratios of 86:14, 70:30, and 48:52. Also, nonwovens obtained from a blend of PDLGA and PVA were used to analyze the effect of the addition of the hydrophilic polymer on degradation and, thus, the release rate. The comprehensive analysis of the developed nonwovens was conducted through an evaluation of the morphology, in vitro degradation, and drug release process, as well as cytotoxicity. It has been observed that all kinds of the developed PDLGA nonwovens provide an extended-release profile but with different release rates, which depend on the comonomer unit ratio and molar mass of the copolymer. Moreover, the increase in hydrophilicity caused by PVA sufficiently accelerates PTX release. The biological activity of released PTX was confirmed under in vitro and in vivo conditions against 4T1 mouse mammary carcinoma. The results of the study enabled us to gain insight into the influence of polymer choice on PTX release from PDLGA ES implants, which may be helpful in their easier translation into the clinic and for better adjustment of the PTX dose for individual treatment. Full article

Niosomes (NIOs), a class of nanovesicular drug delivery system, have garnered significant attention due to their unique architecture, resulting from the self-assembly of non-ionic surfactants (with or without cholesterol) in aqueous media. This bilayered structure enables the encapsulation of both hydrophilic agents in the aqueous core and lipophilic compounds within the lipid bilayer, offering remarkable versatility in therapeutic applications. This article provides an overview of the key principles underlying niosomal formulations, including their composition, preparation methods, formulation conditions and the critical physicochemical parameters influencing vesicle formation and performance. Special emphasis is placed on recent innovations in surface and content modifications that have led to the development of stimuli-responsive niosomal systems, with precise and controlled drug release. These smart carriers are designed to respond to endogenous stimuli (such as pH variations, redox gradients, enzymatic activity, or local temperature changes in pathological sites), as well as to exogenous triggers (including light, ultrasound, magnetic or electric fields, and externally applied hyperthermia), thereby enhancing therapeutic precision. These surface and content modulation strategies effectively transform conventional NIOs into intelligent, stimuli-responsive platforms, reinforcing their innovative role in drug delivery and highlighting their significant potential in the development of smart nanomedicine. 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

Pain management remains a major clinical challenge, as conventional opioids and local anesthetics suffer from short analgesic duration, systemic toxicity, and dependence risks. Advanced drug delivery systems, particularly hydrogels and liposomal bupivacaine, have emerged as promising solutions to address these limitations. Hydrogels, composed of cross-linked hydrophilic polymer networks, enable biocompatible, biodegradable, and sustained drug release, while liposomal bupivacaine encapsulates the anesthetic within lipid vesicles to prolong local analgesia and minimize systemic toxicity. The combination of these systems offers synergistic benefits, including extended drug retention, enhanced efficacy, and reduced opioid reliance. However, clinical translation remains constrained by formulation instability, high production costs, variable patient responses, and stringent regulatory requirements. This review provides a comprehensive overview of current advances in hydrogel and liposomal bupivacaine technologies, highlighting their clinical potential, ongoing challenges, and future directions toward safer, more effective, and personalized pain management strategies. Full article

Τhe self-assembly behavior of a series of amphiphilic diblock copolymers, each consisting of a hydrophilic poly(N-vinyl pyrrolidone) (PNVP) block and a hydrophobic block derived from n-alkyl vinyl esters, namely poly(vinyl butyrate) (PVBu), poly(vinyl decanoate) (PVDc), and poly(vinyl stearate) (PVSt), in aqueous solutions was investigated. Dynamic and static light scattering (DLS and SLS) techniques were employed to monitor the micellization behavior. In addition, the self-assembled structures were observed with Transmission Electron Microscopy (TEM). The effect of the nature of the hydrophobic block, the copolymer composition and the copolymer molecular weight on the self-assembly properties was thoroughly examined. The encapsulation of curcumin and indomethacin within the dry cores of the micellar structures was conducted in aqueous solutions for all block copolymers at various curcumin/indomethacin-to-polymer mass ratios. UV-Vis spectroscopy was used to evaluate the drug-loading capacity and efficiency (%DLC and %DLE). In several cases, the encapsulation of both hydrophobic drugs was found to be nearly quantitative. Combined with the observed stability of the micellar structures, these findings suggest that the block copolymers demonstrate significant potential as carriers for drug delivery applications. Full article

Oleosomes are submicron oil bodies of a triacylglycerol core enveloped by a phospholipid monolayer and embedded proteins, forming a naturally assembled nanocarrier with exceptional oxidative resilience, interfacial stability, and biocompatibility. Their unique architecture supports solvent-free extraction, self-emulsification, and near-complete encapsulation of highly lipophilic compounds (log P > 4), including curcumin and cannabidiol, with reported efficiencies exceeding 95%. These plant-derived droplets enhance oral bioavailability through lymphatic uptake and enable targeted delivery strategies such as magnetically guided chemotherapy, which has reduced tumor burden by approximately 70% in vivo. The review critically examines recent advances in oleosome research, spanning botanical sourcing, green extraction technologies, interfacial engineering, xenobiotic encapsulation, pharmacokinetics, and therapeutic applications across oncology, dermatology, metabolic disease, and regenerative medicine. Comparative analyses demonstrate that oleosomes rival or surpass synthetic lipid nanocarriers in encapsulation efficiency, oxidative stability, and cost efficiency while offering a sustainable, clean-label alternative. Remaining challenges, including low loading of hydrophilic drugs, allergenicity, and regulatory standardization, are addressed through emerging strategies such as hybrid oleosome–liposome systems, recombinant oleosin engineering, and stimulus-responsive coatings. These advances position oleosomes as a versatile and scalable platform with significant potential for food, cosmetic, and pharmaceutical applications. Full article

This study focuses on the preparation of poly(HCQM-co-VP) copolymeric nanoparticles (NPs) to enhance the aqueous solubility and bioavailability of the hydrophobic and antitumor molecules HCQ (hydroxychloroquine) and α-TOS (α-tocopheryl succinate). HCQ is covalently incorporated into the polymer backbone, while α-TOS is encapsulated within the nanoparticles by non-covalent interactions. Poly(HCQM-co-VP) was synthesized from a vinyl derivative of HCQ (HCQM) and N-vinylpyrrolidone (VP), with a molar composition of 17% HCQM and 83% VP, providing the optimal hydrophobic/hydrophilic balance for forming, via nanoprecipitation, empty nanoparticles (NPs) with a diameter of 123.6 nm and a zeta potential of −5.8 mV. These nanoparticles effectively encapsulated α-TOS within their hydrophobic core, achieving an encapsulation efficiency (%EE) of 78%. These α-TOS-loaded NPs resulted in smaller diameters and more negative zeta potentials (71 nm, −19.2 mV) compared to the non-loaded NPs. The cytotoxicity of these NPs was evaluated using the AlamarBlue assay on MCF-7 breast cancer cells. The empty NPs showed no toxic effects within the tested concentration range, after 72 h of treatment. In contrast, the α-TOS-loaded NPs, exhibited a pronounced cytotoxic effect on MCF-7 cells with an IC₅₀ value of 100.2 μg·mL⁻¹, thereby demonstrating their potential as controlled drug delivery systems for cancer treatment. These findings contribute to the development of a new HCQ-based polymeric nanocarrier for α-TOS or other hydrophobic drugs for the treatment of cancer and other diseases treatable with these drugs. Full article

The development of pH-responsive liposomes represents a promising strategy for targeted drug delivery, enhancing therapeutic efficacy while minimizing toxicity and side effects. These innovative nanocarriers are typically synthesized via the thin film hydration method and can be further modified to exhibit stimuli-responsive behavior. pH-responsive liposomes are biocompatible, biodegradable, and capable of encapsulating both hydrophilic and hydrophobic drugs, increasing their versatility in drug delivery. In this mini-review, we explore the mechanism of action of pH-responsive liposomes, analyzing the factors that influence both their intracellular and extracellular behavior. Various formulations are examined, and their characteristics are compared to optimize therapeutic outcomes. Furthermore, we discuss the potential applications in anticancer therapy, in gene therapy, and in bacterial infections as vaccines and diagnostic agents. Full article

Liposomes are nanoscale, spherical vesicles composed of phospholipid bilayers, typically ranging from 50 to 200 nm in diameter. Their unique ability to encapsulate both hydrophilic and hydrophobic molecules makes them powerful nanocarriers for drug delivery, diagnostics, and vaccine formulations. Several FDA-approved formulations such as Doxil^® (Baxter Healthcare Corporation, Deerfield, IL, USA), AmBisome^® (Gilead Sciences, Inc., Foster City, CA, USA), and Onivyde^® (Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) highlight their clinical significance. This review provides a comprehensive synthesis of how molecular dynamics (MD) simulations, particularly coarse-grained (CG) and atomistic approaches, advance our understanding of liposomal membranes. We explore key membrane biophysical properties, including area per lipid (APL), bilayer thickness, segmental order parameter ($S_{CD}$), radial distribution functions (RDFs), bending modulus, and flip-flop dynamics, and examine how these are modulated by cholesterol concentration, PEGylation, and curvature. Special attention is given to curvature-induced effects in spherical vesicles, such as lipid asymmetry, interleaflet coupling, and stress gradients across the leaflets. We discuss recent developments in vesicle modeling using tools such as TS2CG, CHARMM-GUI Martini Maker, and Packmol, which have enabled the simulation of large-scale, compositionally heterogeneous systems. The review also highlights simulation-guided strategies for designing stealth liposomes, tuning membrane permeability, and enhancing structural stability under physiological conditions. A range of CG force fields, MARTINI, SPICA, SIRAH, ELBA, SDK, as well as emerging machine learning (ML)-based models, are critically assessed for their strengths and limitations. Despite the efficiency of CG models, challenges remain in capturing long-timescale events and atomistic-level interactions, driving the development of hybrid multiscale frameworks and AI-integrated techniques. By bridging experimental findings with in silico insights, MD simulations continue to play a pivotal role in the rational design of next-generation liposomal therapeutics. Full article

Background: The encapsulation of hydrophilic drugs within microparticles has gained significant interest in drug delivery systems due to their potential to improve stability, bioavailability, and controlled release of therapeutic agents. Biotin, a water-soluble vitamin, presents challenges such as rapid degradation and limited membrane permeability, which constrain its therapeutic effectiveness. Objectives: This study aims to develop and characterize biotin-loaded microparticles formulated with alginate, Eudragit^® E100, and CaCl₂, and to evaluate their characterization and potential applications. Methods: The microparticles were produced using the external ionic gelation method, where alginate and CaCl₂ solutions were mixed under probe sonication. Eudragit^® E100 was added as a complexing agent. The optimized formulation was used to encapsulate biotin, and various experimental variables were screened to study their influence on the properties of the microparticles. Results: Biotin was encapsulated in alginate microparticles (size: 634 nm; polydispersity index: 0.26; zeta potential: −45 mV) with an encapsulation efficiency of 90.5%. In vitro release studies using vertical diffusion Franz cells demonstrated a controlled release profile following the Weibull kinetic model. Conclusions: Encapsulation techniques offer a promising approach to overcome the limitations of hydrophilic drug delivery. The biotin-loaded microparticles developed in this study have potential applications in both topical and oral formulations, providing controlled release and improved therapeutic efficacy, and illustrate the broader applicability of polymeric encapsulation systems for improving the delivery of labile, hydrophilic bioactives. Full article

Niosomes are nanocarriers with a bilayer structure, consisting of a polar region and a non-polar region. This unique structure allows them to encapsulate compounds with varying polarities, addressing solubility challenges in the transport and delivery of bioactive molecules. The formation of niosomes involves key structural, geometric, and thermodynamic factors influenced by the choice of surfactants and preparation methods. These factors, including the critical packing factor and the hydrophilic–lipophilic balance (HLB), play a crucial role in determining the properties of the final niosomes. Additionally, the use of Tandford’s equations allows for the calculation of geometric parameters. These factors determine the structural integrity and functional properties of niosomes, making it possible to design functional niosomes with characteristics tailored for specific applications. This ability to design niosomes with desired properties is especially valuable in biomedical fields, where precise control over drug delivery and targeting is essential. This review highlights the importance of niosome formulation and presents examples of niosomes that have been functionalized for specific applications, including anticancer treatments, immunological treatments, and their action in the central nervous system. Full article