RSC Pharmaceutics最新文献

{"title":"Sequential- <i>vs</i>. density gradient-centrifugation for the isolation of mitochondria-containing extracellular vesicles.","authors":"Kandarp M Dave, Bodhi T Brady, Balaji Govindaswamy, Vivek S Basudkar, Donna B Stolz, Devika S Manickam","doi":"10.1039/d5pm00316d","DOIUrl":"10.1039/d5pm00316d","url":null,"abstract":"<p><p>A subset of extracellular vehicles (EVs) with particle diameters >200 nm, large vesicles (lEVs), contain mitochondria that increase recipient cell bioenergetics. To date, sequential centrifugation (SC) is the most reported protocol to separate lEVs from the smaller EVs (<200 nm)/exosomes. We have previously demonstrated that lEVs derived from brain endothelial cells (BECs) using the standard SC method transfer their innate mitochondria to recipient BECs, increase recipient BEC bioenergetics, reduce brain infarct volume, and improve sensorimotor functions in a mouse model of transient ischemic stroke. Despite their promising therapeutic activity, SC-isolated lEVs are likely a mixture of mitochondria-containing lEVs and non-mitochondria-containing lEVs. We hypothesized that subsequent purification of SC-isolated lEVs using density-gradient centrifugation (DGC) may yield a purer sample of mitochondria-containing lEVs. We established a DGC protocol to purify lEVs. In this pilot study, lEVs isolated using SC and DGC protocols were compared to determine their physicochemical characteristics and their effects on recipient BEC bioenergetics. SC-lEVs and DGC-lEVs both significantly restored ATP levels in OGD-injured BECs with no difference between groups. However, a Seahorse mitochondrial function assay revealed distinct functional effects: SC-lEVs did not significantly alter respiration, whereas DGC-lEVs induced a dose-dependent increase in oxygen consumption rate, indicating enhanced oxidative phosphorylation. These findings demonstrate that DGC purification yields a more mitochondria-enriched and functionally potent lEV preparation with an enhanced capacity to restore oxidative phosphorylation in post-ischemic BECs.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611689","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":"Co-formulation of IL-12 mRNA and doxorubicin in polymeric nanoparticles for simultaneous delivery in murine melanoma.","authors":"Elina Tanskanen, Hongning Sun, Kai-Chun Cheng, Jun Ishihara, Asha K Patel","doi":"10.1039/d6pm00136j","DOIUrl":"10.1039/d6pm00136j","url":null,"abstract":"<p><p>Liposomal or polymeric nanoparticles have been instrumental in improving the delivery of poorly soluble chemotherapeutics and those with dose limiting toxicity such as doxorubicin (DOX). More recently, nanoformulations have been shown to enable simultaneous delivery of emerging biomolecules such as siRNA. However, for larger nucleic acids such as mRNA, this remains challenging. In this study, we developed a poly(β-amino ester) (PBAE) based platform, capable of co-formulating mRNA and doxorubicin into nanoparticles. To demonstrate proof of concept using therapeutically relevant cargo, immunomodulatory interleukin-12 (IL-12) was selected as a model mRNA. IL-12 is a pro-inflammatory cytokine that promotes anti-tumour immunity partly through amplifying effector cytokines such as interferon-γ (IFNγ). We found that PBAE complexed DOX and mRNA into positively charged nanoparticles of 120 nm and size-exclusion chromatography indicated a DOX loading efficiency of over 97%. Co-association of both DOX and mRNA was characterised at a single nanoparticle level by nano-flow cytometry. Following delivery to B16F10 murine melanoma cells, more than 95% of cells were double-positive for DOX and Cy5-labelled mRNA, and confocal microscopy confirmed co-localised regions of DOX with mRNA. Interestingly, nanoformulated DOX had increased nuclear accumulation by 1.7-fold relative to free DOX, which correlated with a significantly reduced cell viability of 12.9% with PBAE-DOX/mRNA, compared to 26.6% for free DOX at the same dose. Moreover, despite this strong cytotoxic effect, reporter mRNA translation remained robust, with luciferase expression approximately two orders of magnitude above non-transfected controls at the highest DOX doses. Co-formulation of <i>IL-12</i> mRNA and DOX with PBAE demonstrated effective IL-12 protein secretion in transfected B16F10 cells with a simultaneous DOX dose dependent reduction in viability. Secreted IL-12 was bioactive, inducing dose-dependent STAT4 phosphorylation and IFNγ secretion in primary mouse splenocytes. Furthermore, in a syngeneic melanoma mouse model, intratumoural administration of PBAE-DOX/<i>IL-12</i> mRNA achieved significantly elevated levels of IL-12 and IFNγ in the tumour compared to the saline control, confirming delivery of DOX, as well as IL-12 protein secretion, and immunostimulatory activity <i>in vivo</i>. These findings demonstrate that PBAE is a promising platform for co-delivery of cytokine encoded mRNA with DOX in a single formulation, establishing feasibility for advanced chemoimmunotherapy approaches.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458318","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":"Dual-adjuvant mucosal vaccine leveraging mast cell and TLR9 agonists for protection against poxvirus infection.","authors":"Connor T Murphy, Grace L Williamson, Luis Ontiveros-Padilla, Aaron T Hendricksen, Brandi T Johnson-Weaver, Hae Woong Choi, David M Gooden, Santhosh Kalpathy, Alexandra M Lopez, Erik S Pena, Jacob M Bachelder, Rani S Sellers, Soman N Abraham, Herman F Staats, Kristy M Ainslie","doi":"10.1039/d5pm00380f","DOIUrl":"10.1039/d5pm00380f","url":null,"abstract":"<p><p>Mast cells (MC) are innate immune cells that are predominantly localized under the skin and at mucosal surfaces, and play a role in numerous physiological processes, including host response to pathogens. Recently, mast cell activators (MCA) have been identified as mucosal vaccine adjuvants that are able to promote a strong and antigen-specific immune response. We performed an extensive structure-activity relationship (SAR) analysis on the previously identified small molecule MCA, ST101036, to further optimize its adjuvanticity. This led to the development of the derivative, VAP-1185, which demonstrated improved mast cell degranulation activity <i>in vitro</i>, and a Th2-biased <i>in vivo</i> immune response. While mucosal vaccines with a single adjuvant have shown effectiveness, combining two adjuvants can activate multiple immune pathways, leading to a stronger and more comprehensive immune response. Additionally, dual adjuvant vaccines can elicit a balanced Th1/Th2 response, leading to equally effective cellular and humoral responses. We combined VAP-1185 with the FDA-approved adjuvant, cytosine phosphoguanine (CpG), which activates toll-like receptor 9 (TLR9) and promotes a Th1-biased immune response. This dual adjuvant formulation promotes inflammatory cytokine production <i>in vitro</i>, additive humoral effects and an active cellular response <i>in vivo</i>, as well as a favorable safety profile when intranasally administered to C57BL/6 mice. Subsequently, this adjuvant formulation was also able to confer protection against a lethal challenge of vaccinia virus in BALB/c mice. Thus, we report a novel mucosal vaccine formulation that produces an effective Th1/Th2 balanced immune response.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"1022-1033"},"PeriodicalIF":5.5,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229984","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":"Nanoparticle vaccine formulations for dengue virus.","authors":"Connor T Murphy, Kristy M Ainslie","doi":"10.1039/d6pm00015k","DOIUrl":"10.1039/d6pm00015k","url":null,"abstract":"<p><p>Dengue virus (DENV) is one of the most prevalent mosquito-borne pathogens, with almost half of the global population at risk of infection. While most cases are mild, severe illness and even death is not uncommon. There are currently a lack of available antivirals and highly effective prophylactic vaccines available for DENV, leading to a significant gap in protection. While live-attenuated vaccines have been developed and briefly utilized, some have been found to increase the risk for developing antibody-dependent enhancement (ADE), a phenomenon that can worsen outcomes in those who are exposed to DENV after receiving the vaccination. Nanoparticle-based vaccine formulations provide numerous advantages over live-attenuated vaccines such as controlled release, dose-sparing, and ability to effectively encapsulate adjuvants and viral antigens, while simultaneously minimizing the risk for development of ADE. Numerous carrier systems have been developed, including polymeric, lipid, inorganic, and protein-based formulations. Each system has been found to induce unique antigen-specific immune activation that includes varying degrees of humoral and cellular immune responses. While there is still much research to be done, nanoparticle-based vaccine formulations offer a promising approach to combat the growing threat of DENV.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" ","pages":"935-954"},"PeriodicalIF":5.5,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201974","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":"Biogenic chitosan anchored Cu2O/ZnO nanocomposite: unlocking synergy for drug delivery, antineoplastic action, and wound repair","authors":"Manojna R. Nayak, Ravindra R. Kamble, Lokesh Bheemayya, Vishwa B. Nadoni, Amruta Patri, Mallika Wali, Arun K. Shettar, Joy H. Hoskeri, Rangappa S. Keri and Ashok M. Sajjan","doi":"10.1039/D5PM00392J","DOIUrl":"https://doi.org/10.1039/D5PM00392J","url":null,"abstract":"<p >The clinical efficacy of many chemotherapeutic agents is often limited by inefficient drug delivery, poor selectivity toward cancer cells, and insufficient support for tissue regeneration. To address these challenges, we report the green synthesis of a multifunctional chitosan-anchored Cu<small>₂</small>O/ZnO nanocomposite (CS-Cu<small>₂</small>O/ZnO NC) using water calyx fluid (WCF) extracted from <em>Spathodea campanulata</em> flower buds as a natural reducing and stabilizing agent. Structural and physicochemical characterization using X-ray diffraction confirmed the crystalline phases of Cu<small>₂</small>O and ZnO, while UV-Vis spectroscopy showed characteristic absorption in the 270–320 nm region indicating nanoparticle formation. FTIR analysis verified the successful integration of chitosan and phytochemical functional groups with metal oxides. Transmission electron microscopy revealed quasi-spherical nanoparticles uniformly distributed within the polymer matrix with an average particle size of 20–40 nm, whereas dynamic light scattering showed a hydrodynamic diameter of ∼89.3 nm with a zeta potential of −29.4 mV, confirming good colloidal stability. The nanocomposite was employed as a carrier for cisplatin and exhibited high drug loading efficiency with a biphasic release profile, achieving 94.88% cumulative drug release over 72 h. <em>In vitro</em> cytotoxicity studies demonstrated enhanced anticancer activity against A375 skin cancer cells (IC<small>₅₀</small> = 29.84 µg mL<small>⁻¹</small>) with comparatively lower toxicity toward L929 fibroblast cells. Furthermore, scratch wound healing assays revealed significant fibroblast cell migration and accelerated wound closure within 24 h, highlighting the regenerative potential of the nanocomposite. Overall, the developed green-synthesized CS-Cu<small>₂</small>O/ZnO nanocomposite represents a sustainable multifunctional platform for controlled drug delivery, cancer therapy, and wound healing applications.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 778-798"},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00392j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148011755","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":"In vivo translation of a dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles for the co-delivery of camptothecin and 5-fluorouracil","authors":"Debatrayee Dasgupta, Sonal Thakore, Anjali Patel and Sriram Seshadri","doi":"10.1039/D5PM00390C","DOIUrl":"https://doi.org/10.1039/D5PM00390C","url":null,"abstract":"<p >With the advent of nanotechnology, combined drug therapies employing dual-drug delivery provide an efficient way to overcome the drawbacks of conventional chemotherapy, such as lack of specificity, multidrug resistance and low aqueous solubility. Herein, a dual-drug delivery system based on mesoporous silica nanoparticles (MSNs) was developed to target tumours with the dual-responsive co-delivery of two anticancer drugs, camptothecin (CPT) and 5-fluorouracil (5-FU), in a sequential manner. The mesopores were loaded with CPT, and subsequently, a pegylated-biotin polymer was used to coat them. The disulphide link and acid group present in the polymer contribute to the stimuli-triggered release of the drugs. Since cancer cells need biotin to continue proliferating, it functions as a targeting ligand. Mathematical modelling studies revealed that the drug-release kinetics followed a diffusion mechanism for both the hydrophobic and hydrophilic drugs. Beyond <em>in vitro</em> release and cytotoxicity assays, extensive <em>in vivo</em> biological evaluations, including liver function markers, serum biochemistry and histopathological examinations, demonstrated pronounced tumour suppression with reduced hepatic toxicity. The nanocarrier downregulated key tumour biomarkers, effectively lowered serum transaminases and restored normal liver architecture. Collectively, these findings affirm the translational potential of this smart dual-drug delivery platform for cancer therapy.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 738-748"},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00390c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148011752","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":"Correction: Enhancing the bioavailability of sparingly-soluble drugs by expandable, solid-solution fibrous dosage forms","authors":"Aron H. Blaesi, Henning Richter and Nannaji Saka","doi":"10.1039/D6PM90005D","DOIUrl":"https://doi.org/10.1039/D6PM90005D","url":null,"abstract":"<p >Correction for ‘Enhancing the bioavailability of sparingly-soluble drugs by expandable, solid-solution fibrous dosage forms’ by Aron H. Blaesi <em>et al.</em>, <em>RSC Pharm.</em>, 2026, <strong>3</strong>, 88–102, https://doi.org/10.1039/D5PM00195A.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 820-820"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d6pm90005d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148011758","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":"Merged in silico–in vitro validations of atenolol and amlodipine besylate with excipient interactions for the design of solid oral dosage forms","authors":"Gaurav Awasthi and Subham Banerjee","doi":"10.1039/D6PM00014B","DOIUrl":"https://doi.org/10.1039/D6PM00014B","url":null,"abstract":"<p >Early understanding and estimation of interactions between drugs and excipients is a crucial step in preformulation studies. <em>In silico</em> studies utilising computational methods were followed by <em>in vitro</em> studies and analytical validation to identify stable excipients (SmartEx and Ludipress) for the development of solid oral dosage forms. <em>In silico</em> studies were conducted using the FormulationDE machine learning tool, which utilises artificial intelligence to interpret input data. FormulationDE can predict compatibility outcomes based on functional groups using SHAP (Shapley Additive explanations) force plots. <em>In vitro</em> studies, including isothermal stress testing methods, ATR-FTIR, DSC and drug stability profiles, were conducted to assess the potential for DEIs under long-term storage and physiological conditions. These studies were demonstrated, and samples were analysed using high-performance liquid chromatography to quantify the percentage of drug degradation over time. The <em>in silico</em> studies showed that ATN was compatible with lactose and mannitol, whereas AMB was incompatible with both. The <em>in vitro</em> IST results showed that ATN was compatible with SmartEx, whereas AMB was incompatible with Ludipress and SmartEx. Drug stability profiles were obtained under gastric pH (1.2) and incubation at 37 °C for four hours to evaluate the resilience of the drugs under physiological conditions and to mimic the gastric environment. The drug stability profiles showed that AMB was unstable and ATN was stable under the gastric physiological conditions. This article highlights the importance of integrating <em>in silico</em> with <em>in vitro</em> experimental techniques in preformulation to minimise risk during later stages of formulation development. The results of various studies will guide the future development of ATN-based solid oral dosage forms using SmartEx QD 100 thermoplastic excipients.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 768-777"},"PeriodicalIF":0.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d6pm00014b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148011754","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":"Enhancing the performance of granisetron HCl orodispersible tablets using co-processed MCC-mannitol excipients: a direct compression approach","authors":"Shazia Naseem Chaudhry and Atiq Ur Rahman","doi":"10.1039/D5PM00276A","DOIUrl":"https://doi.org/10.1039/D5PM00276A","url":null,"abstract":"<p >Orodispersible tablets (ODTs) are favored for their rapid disintegration in the mouth without the need for water, thereby improving patient compliance, particularly in dysphagic, geriatric, and oncology patients. Advanced manufacturing technologies like Orasolv®, Durasolv®, and Zydis® offer unique benefits but are generally associated with high costs and intricate processes. Common manufacturing approaches include molding, freeze-drying, and direct compression, with the latter being the most economical and industrially practical method. The present study aimed to develop granisetron HCl ODTs using a laboratory-prepared co-processed excipient system composed of microcrystalline cellulose (MCC) and mannitol. The system was developed by combining the excipients at the sub-particle level to enhance flowability and compressibility, rather than relying on commercially available multifunctional excipients. The performance of this co-processed MCC–mannitol system was systematically compared with that of the corresponding physical mixtures. Granisetron HCl is a 5-HT3 receptor antagonist commonly prescribed to manage nausea and vomiting induced by chemotherapy. It is well-suited for ODTs due to its low dosage requirements and water solubility. In the formulations, microcrystalline cellulose and mannitol were used as bulking agents and sodium starch glycolate (SSG) and crospovidone (CP) as superdisintegrants. The performance of co-processed excipients was compared with that of physical mixtures. Precompression parameters, including the angle of repose and compressibility index, along with post-compression characteristics such as wetting time, water absorption ratio, disintegration time, and <em>in vitro</em> drug release, were evaluated. Among the tested formulations, formulation F7 containing 4% crospovidone and co-processed MCC–mannitol exhibited the most favorable performance, with a rapid disintegration time of 10 ± 0.12 s and 98.14% ± 0.25% drug release within 180 s. Comparative evaluation demonstrated that the co-processed excipient system provided improved powder flow and tablet performance relative to the physical mixtures. These findings indicate that at the sub-particle level, the co-processing of conventional excipients can be an effective and practical strategy to enhance the ODT performance using a cost-effective direct compression approach.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 809-819"},"PeriodicalIF":0.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00276a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148011757","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":"Polymer-lipid hybrid nanoparticles co-encapsulating fucoxanthin and carbon dots for targeted anti-inflammatory therapy in Alzheimer's disease","authors":"J. Horacio Silvestre-Martínez, Lorna G. Yañez-Algandar, Karina del Carmen Lugo-Ibarra and Ana B. Castro-Ceseña","doi":"10.1039/D6PM00008H","DOIUrl":"https://doi.org/10.1039/D6PM00008H","url":null,"abstract":"<p >Alzheimer's disease (AD) is a long-term brain disorder characterized by the buildup of proteins like amyloid-beta (Aβ) and Tau. This disease process can start up to 20 years before symptoms such as memory loss, language problems, changes in personality, and eventually dementia appear. Currently, AD has no cure, and available treatments only ease symptoms, making it a major global health concern. Developing new therapies is urgently needed. Nanomedicine presents promising solutions, especially for overcoming challenges like delivering drugs across the blood–brain barrier (BBB). In this study, we explored polymer-lipid hybrid nanoparticles (NPs) decorated with transferrin (Tf) to help them cross the BBB. These NPs were loaded with carbon dots (CDs) and fucoxanthin (Fx), which have antioxidant and anti-inflammatory qualities that may benefit neurodegenerative disease treatment. The resulting nanoparticle formulation (NPs-CDFx) had encapsulation efficiencies of 45% for Fx and 10% for CDs, with an average particle size of about 88.74 nm. The safety of these NPs was tested using an <em>in vitro</em> model with lipopolysaccharide (LPS) stimulated rat astrocytes, where high cell viability (92.18%) was observed. qPCR analysis showed that NPs-CDFx significantly lowered the expression of genes linked to neuroinflammation and disease progression, such as APP, GFAP, and S100β. To further confirm delivery, the NPs were injected into five-day-old zebrafish larvae, where confocal microscopy detected the CDs’ fluorescence in the brain, indicating successful targeted delivery across the BBB. Overall, these findings suggest that the nanoparticles can efficiently deliver therapeutic agents to the brain, reduce neuroinflammatory gene expression, and demonstrate the effectiveness of polymer-lipid hybrid nanoparticles for targeted brain drug delivery.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 669-681"},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d6pm00008h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148011766","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}