{"title":"Electrospun nanofibers for route-specific pharmacokinetic modulation: Mechanistic insights, evidence gaps, and translational challenges","authors":"Alireza Maboudi, Mahdi Soltanoghli, Mohammadmahdi Ghavamipour Komleh","doi":"10.1016/j.onano.2026.100312","DOIUrl":"10.1016/j.onano.2026.100312","url":null,"abstract":"<div><div>Electrospun nanofibers function not simply as release matrices, but as structural determinants of route-specific pharmacokinetic input and exposure. This review analyzes how nanofiber architecture, polymer composition, and drug-matrix interactions reshape route-specific pharmacokinetic behavior. Mechanistically, nanofibers influence pharmacokinetics by modifying dissolution rate, stabilizing amorphous drug states, regulating input functions, enhancing barrier interaction, and enabling localized depot formation. These effects translate into measurable pharmacokinetic outcomes, reduced fluctuation index, and decoupling of local tissue exposure from plasma concentrations.</div><div>Mapping mechanistic design variables to dominant biological bottlenecks reveals that pharmacokinetic performance is fundamentally route-dependent. While oral systems frequently enhance systemic exposure through dissolution-driven absorption, mucosal and implantable nanofibers more commonly engineer spatially controlled local exposure with limited systemic spillover. Current in vivo evidence supports these route-specific pharmacokinetic advantages but remains heterogeneous, with limited systematic pharmacokinetic evaluation, weak in vitro-in vivo correlation, and minimal integration of physiologically based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PK-PD) modeling.</div><div>This review introduces a route-aware pharmacokinetic design framework that integrates nanofiber architecture, biological bottlenecks, and graded levels of PK evidence to guide rational exposure engineering. The paper should be read as a mechanistic framework for organizing current evidence, rather than as a systematically conducted evidence synthesis. By positioning electrospun nanofibers as pharmacokinetic input-function shaping systems, this review proposes a route-aware design and evidence framework to guide rational development and translational assessment of nanofiber-mediated drug exposure.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"30 ","pages":"Article 100312"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148566278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering organic-organic and organic-inorganic nanohybrids for Drug Delivery","authors":"Valentina Pacciani , Deborah Bonavolontà , Jacopo Cardellini , Lucrezia Caselli , Arianna Balestri , Debora Berti","doi":"10.1016/j.onano.2026.100305","DOIUrl":"10.1016/j.onano.2026.100305","url":null,"abstract":"<div><div>Hybrid nanoparticles (HNPs) are emerging as cutting-edge materials in nanomedicine, offering unique opportunities for drug delivery, diagnostic imaging, and therapeutics. By harnessing interactions between organic or inorganic components, these systems achieve precise control over size, surface, and functional properties. The synergy between different building blocks enables enhanced biocompatibility, targeted delivery, and stimuli-responsive functions that are challenging to achieve with single-component systems. This review highlights the state of the art in organic–organic and organic–inorganic nanohybrids, focusing on recent advances for drug delivery applications. Examples include organic-organic hybrids combining lipids, polymers, and biological constituents, <em>e.g.</em>, extracellular vesicle- or cell membranes-derived components, as well as inorganic NPs hybridized with polymers, peptides, or lipids. We further discuss current challenges and future perspectives in the field, including hybrids that are responsive to internal or external triggers, which hold significant promise for advancing personalized medicine and translating nanomedicine innovations into the clinic.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"29 ","pages":"Article 100305"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing diabetic wound healing: The emerging role of solid lipid nanoparticles in targeted nano therapy","authors":"Ashutosh Gupta , Soji Soman , Sandesh Ramchandra Jadhav , Disha Marwaha , Praveen Halagali , Moumita Saha , Srinivas Mutalik , Sudheer Moorkoth , Namdev Dhas , Vamshi Krishna Tippavajhala , Aditya Dev Rajora","doi":"10.1016/j.onano.2026.100304","DOIUrl":"10.1016/j.onano.2026.100304","url":null,"abstract":"<div><div>Diabetic wounds stand as one of the most severe conditions of diabetes, which can be transformed into chronic, non-healing ulcers and may increase the risk of limb amputation. These complications can be prevented using a novel targeted treatment approach. In recent years, nanoformulation has emerged as a promising technique for addressing such complications. Solid lipid nanoparticles (SLNs) have attracted substantial interest due to their biocompatibility, stability, and ability to load a wide range of therapeutic agents. This review summarizes synthesis strategies and recent advancements in SLNs for the treatment of diabetic wounds. The lipid matrix of the SLNs is essential for their biocompatibility and for the encapsulation of a wide range of bioactive agents, such as growth factors. The SLNs also possess a high zeta potential and interfacial charge, which improve their stability in biological fluids and influence their interactions with the wound environment. We have also highlighted the different methods for synthesizing SLNs, including microemulsion methods, supercritical fluid methods, spray drying, etc., depending on the route of administration. The SLNs can be administered through the topical, oral, and systemic routes. The topical application of bioactive compounds loaded into SLNs helps reduce microbial load and oxidative stress at the diabetic wound site. However, oral and systemic delivery help manage oxidative stress associated with diabetes, and at the wound site, they provide a dual approach for managing the diabetic wound. Overall, SLNs represent a promising platform for the effective treatment of diabetic wounds, offering multifunctional strategies to overcome current therapeutic limitations.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"29 ","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147858758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OpenNanoPub Date : 2026-03-01Epub Date: 2026-01-27DOI: 10.1016/j.onano.2026.100283
Denisse Gardea-Gutiérrez , Manuel Román-Aguirre , Raúl Loera-Valencia , Blanca Sánchez-Ramírez , Yocanxóchitl Perfecto-Avalos , Silvia L. Montes-Fonseca
{"title":"Flexible asymmetric liposomes as a platform for improved plasmid DNA delivery: An in vitro study","authors":"Denisse Gardea-Gutiérrez , Manuel Román-Aguirre , Raúl Loera-Valencia , Blanca Sánchez-Ramírez , Yocanxóchitl Perfecto-Avalos , Silvia L. Montes-Fonseca","doi":"10.1016/j.onano.2026.100283","DOIUrl":"10.1016/j.onano.2026.100283","url":null,"abstract":"<div><div>As a versatile type of nanocarrier, liposomes have gained attention due to their biocompatibility, biodegradability, and ability to encapsulate a wide range of compounds. Asymmetric liposomes are characterized by distinct lipid compositions in their inner and outer layers, enhancing drug encapsulation and stability. Surfactant compounds and ethanol confer the flexibility of liposomes in their lipid layer. This characteristic allows liposomes to deform without breaking or releasing their contents, enabling them to cross complex barriers, such as the skin. This research investigates the innovative design and application of flexible asymmetric liposomes for transdermal DNA delivery. By using an adapted inverse emulsion technique, this study successfully encapsulated plasmid DNA within flexible asymmetric liposomes to evaluate its biocompatibility and skin permeation capacity in an in vitro model. Several formulations of liposomes containing DOTMA, DOPE, and/or cholesterol as the inner layer and DSPC, Span80, and/or ethanol as the outer layer were assessed through viability assay, transfection efficiency, and permeability testing using the Parallel Artificial Membrane Permeability Assay (PAMPA). All formulations demonstrated over 69% cell viability at a concentration of 5 μg, and transfection efficiency was significantly enhanced, reaching transfection rates of 32.37% ±3.32% in liposomes with all components. Permeability testing showed that the liposomal formulations exhibited high permeability, further improved by including ethanol and surfactants. Key findings indicate that cholesterol, Span 80, and ethanol substantially contribute to transfection rates and permeation. This research underscores the potential of flexible asymmetric liposomes for effective transdermal delivery of genetic material.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"28 ","pages":"Article 100283"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OpenNanoPub Date : 2026-03-01Epub Date: 2026-02-23DOI: 10.1016/j.onano.2026.100291
Ozge Cinar, Ilgin Kimiz-Gebologlu, Sevval Kurt, Suphi S. Oncel
{"title":"Microalgae-derived biomolecule and nanoparticle conjugates: Emerging therapeutic platforms for cancer treatment","authors":"Ozge Cinar, Ilgin Kimiz-Gebologlu, Sevval Kurt, Suphi S. Oncel","doi":"10.1016/j.onano.2026.100291","DOIUrl":"10.1016/j.onano.2026.100291","url":null,"abstract":"<div><div>Nanoparticle-based drug delivery systems have the potential to provide a promising platform for overcoming the limitations of therapeutics in cancer treatment, thanks to advantages such as controlled release, tumor targeting, and reduced systemic toxicity. In parallel, microalgal biomolecules possess strong antioxidant and antiproliferative properties. However, these biomolecules are therapeutically limited due to their low stability and restricted bioavailability. The approach of using microalgal compounds in combination with nanoparticles both improves their pharmacokinetic properties and enhances multiple anticancer mechanisms (ROS modulation, caspase activation, etc.). This review focuses on the anticancer potential of microalgal biomolecules and nanoparticulate systems, the intracellular mechanisms of action of the conjugated platforms they form, and their biocompatibility advantages. It also describes the potential of conjugated platforms for future clinical applications, highlighting their importance as biologically synergistic and targeted next-generation therapeutic platforms in cancer treatment.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"28 ","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OpenNanoPub Date : 2026-03-01Epub Date: 2025-12-28DOI: 10.1016/j.onano.2025.100280
Berenice Erendira Oseguera-Guerra , Oliver Lopez-Villegas , Manuel Román-Aguirre , Alfredo Aguilar-Elguezabal , Raúl Loera-Valencia , Silvia Lorena Montes-Fonseca
{"title":"Enantiomeric lysine-based cationic lipids: Design, synthesis, and characterization for in vitro gene delivery","authors":"Berenice Erendira Oseguera-Guerra , Oliver Lopez-Villegas , Manuel Román-Aguirre , Alfredo Aguilar-Elguezabal , Raúl Loera-Valencia , Silvia Lorena Montes-Fonseca","doi":"10.1016/j.onano.2025.100280","DOIUrl":"10.1016/j.onano.2025.100280","url":null,"abstract":"<div><div>Nucleic acid delivery is crucial for gene therapy, vaccination, and cancer treatment. Despite advances in cationic lipid-based vectors, their transfection efficiency is often limited by structural complexity. In this study, we synthesized lysine-based cationic lipids by esterifying <span>d</span>- or <span>l</span>-lysine with alcohols of varying chain lengths. The compounds were characterized by infrared spectroscopy and mass spectrometry, incorporated into liposomes, and evaluated for transfection efficiency, particle size, morphology, and cytotoxicity <em>in vitro.</em> Transfection performance increased with chain length, peaking at 20 carbons, with no significant differences between <span>d</span>- and <span>l</span>-enantiomers. Compared to Lipofectamine 2000, the optimized liposomes showed superior gene delivery while preserving cell viability. They displayed predominantly spherical to oval morphologies, particle sizes of 30–130 nm, and negligible cytotoxicity. These results suggest lysine-based cationic lipids are promising, safe, and effective nonviral vectors for nucleic acid delivery.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"28 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OpenNanoPub Date : 2026-03-01Epub Date: 2026-02-17DOI: 10.1016/j.onano.2026.100290
Asmaa M. Elsherbini, Shaymaa A. Mohamed, Aya M. Zayed, Wafaa A. Mohamed, Sally A. Sabra
{"title":"Obesity-associated pathologies: Recent advances in stimuli-responsive nanocarriers for adipose tissue browning and beyond","authors":"Asmaa M. Elsherbini, Shaymaa A. Mohamed, Aya M. Zayed, Wafaa A. Mohamed, Sally A. Sabra","doi":"10.1016/j.onano.2026.100290","DOIUrl":"10.1016/j.onano.2026.100290","url":null,"abstract":"<div><div>Obesity is a chronic multifactorial disorder affecting more than 600 million people worldwide. It is initially caused by an imbalance between energy intake and consumption, and it is strongly correlated to many chronic and life-threatening disorders such as cardiovascular diseases, digestive diseases, colorectal cancer, and others. Obesity can be primarily managed via changing caloric consumption and including physical activity in the daily routine. Another solution is pharmacological therapies such as appetite suppressors and glucagon-like peptide-1 receptor agonists. Surgical intervention is also an available solution, but it is invasive, whereas changing caloric consumption or physical activity usually affords poor outcomes. Browning agents can convert WATs (white adipose tissues, energy-storing cells) into BATs (brown adipose tissues, energy-expending cells), which is an effective approach to reduce body weight. However, most of the available browning agents, either synthetic or natural, suffer from several drawbacks ranging from poor aqueous solubility to severe cardiovascular toxicity. As a result, more innovative approaches can be utilized, which can target obesity, such as passively targeted nanocarriers, depending on their lipophilicity or cationic nature. Actively targeted nanocarriers can target obesity depending on endothelial, adipocyte, or macrophage-based targeting. However, most recent research has transferred to develop more precise stimuli-responsive nanocarriers that can provide an on-demand drug release in response to different stimuli, either intrinsic or extrinsic. In this review, the most recent advances in stimuli-responsive nanocarriers in managing obesity and some of its related disorders including cardiovascular diseases and colorectal cancer, will be discussed.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"28 ","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OpenNanoPub Date : 2026-03-01Epub Date: 2026-02-11DOI: 10.1016/j.onano.2026.100288
Shriraj B. Patel, Dhanashree P. Sanap
{"title":"Scaling up nanoformulation manufacturing: A multi–case study linking target product profiles, critical quality attributes, and quality by design","authors":"Shriraj B. Patel, Dhanashree P. Sanap","doi":"10.1016/j.onano.2026.100288","DOIUrl":"10.1016/j.onano.2026.100288","url":null,"abstract":"<div><div>Nanoformulation platforms have transformed drug delivery; however, reliable scale-up from laboratory to manufacturing remains the principal barrier to clinical translation. This review integrates target product profile (TPP)–driven requirements with critical quality attributes (CQAs), platform-specific unit operations, and Quality by Design (QbD) principles to analyze scalable manufacturing of five major nanoformulation classes—lipid/liposome, polymeric/micellar, nanoemulsion, nanocrystal, and albumin/biopolymer systems—which collectively represent over 80 % of clinically approved nanomedicines. Quantitative analysis across these platforms demonstrates that controlled micromixing and solvent displacement routinely yield lipid and polymeric nanoparticles in the 50–200 nm range, while energy density–constrained high-pressure homogenization governs droplet size distributions in nanoemulsions, and stress intensity and stabilizer adsorption dictate nanocrystal quality. Protein-based carriers are shown to be particularly sensitive to raw-material variability and crosslinking kinetics. Five industrial case studies (Doxil®/CAELYX®, Onpattro®, Comirnaty®, Abraxane®, and AmBisome®) illustrate how orthogonal analytics (e.g., DLS and AF4–MALS), closed single-use architectures, and digitally enabled QbD–PAT frameworks link critical process parameters (CPPs) to robust control strategies across development and commercial manufacture. Overall, the review highlights standardization, quantitative comparability, and data-driven control as central enablers of scalable and regulatory-ready nanomedicine manufacturing.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"28 ","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Formulation, characterization, and valorization of the antioxidant, antibiofilm, and anti-adhesion potentials of a clove essential oil nanoemulsion","authors":"Enis Ben Bnina , Jihen Missaoui , Mohamed Firas Gannouni , Lotfi Achour , Badr Bahloul","doi":"10.1016/j.onano.2026.100286","DOIUrl":"10.1016/j.onano.2026.100286","url":null,"abstract":"<div><div>Food safety and control are fundamental public health issues that maintain consumer confidence and protection. This design (management) requires monitoring production, processing, and conservation processes while limiting microbiological, chemical, and physical risks. In this context, clove essential oil, a bioactive essence with a broad spectrum of biological activities, is increasingly studied as a natural biopreservative in innovative food safety strategies. This study reports the encapsulation of this oil into a nanoemulsion at concentrations of 10 mg/mL, 1 mg/mL, and 0.1 mg/mL. Dynamic light scattering, zeta potential, polydispersity index, and particle size all demonstrated optimal morphology and a stable system.</div><div>The nanoformulation significantly improves the antioxidant activity of clove essential oil, even at high dilutions, while protecting the degradation of natural active ingredients and ensuring controlled release. This nanoemulsion exhibits a moderate antimicrobial effect against various resistant pathogenic bacteria and fungi. However, at a concentration of 10 mg/mL, it showed a 100 % antibiofilm effect against both Gram-positive and Gram-negative bacteria. This nanoemulsion demonstrated significant potential to prevent surface adhesion against all bacteria tested, except <em>L. monocytogenes</em>.</div><div>This research reveals crucial information about an innovative natural nanoemulsion for food safety and control, unveiling its antioxidant, anti-adhesive, and anti-biofilm potential against resistant pathogens. These results represent a promising step forward in reducing contamination risks and extending shelf life without altering organoleptic properties, offering environmental benefits and hygiene practices while targeting sustainable industrial applications to increase food safety.</div></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"28 ","pages":"Article 100286"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}