RSC Pharmaceutics最新文献

{"title":"Advancing sustainability through digitalization: from drug development to patient care","authors":"Remo Eugster and Paola Luciani","doi":"10.1039/D5PM00342C","DOIUrl":"https://doi.org/10.1039/D5PM00342C","url":null,"abstract":"<p >Digitalization is transforming the pharmaceutical industry, offering innovative solutions to enhance sustainability across the pharmaceutical value chain. From drug discovery to patient care, digital tools such as artificial intelligence (AI), machine learning (ML), blockchain, and digital twins optimize processes, reduce resource use, and mitigate environmental and social impacts. In drug discovery, AI accelerates and optimizes research while green chemistry initiatives prevent toxic waste. During manufacturing, predictive maintenance and quality control boost efficiency, and digital tools ensure secure, traceable distribution and enhance supply chain transparency. Within clinical care, AI-driven personalized medicine improves patient outcomes and reduces inefficiencies, while digital health records, diagnostics, and therapies promote healthcare equity and expand access. Collectively, these innovations align the industry with global sustainability goals, advancing a pharmaceutical ecosystem that is more efficient, environmentally responsible, and socially just. Yet challenges in energy demand, data equity, and regulatory adaptation must be addressed to tap into the full potential of a digital transformation.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 361-373"},"PeriodicalIF":0.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00342c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558601","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":"Fucoidan/bis-MPA-based dendrimer nanoparticles with intrinsic anti-angiogenic activity for oncology applications","authors":"Filipe Olim, Ana Duarte, Ana Rute Neves, Irene Rodriguez-Clemente, Joel T. Kidgell, Barbara C. Wimmer, Valentín Ceña and Helena Tomás","doi":"10.1039/D5PM00362H","DOIUrl":"https://doi.org/10.1039/D5PM00362H","url":null,"abstract":"<p >Nanoparticles with intrinsic anti-angiogenic activity hold strong promise in cancer nanomedicine, as they can both help suppress metastasis and deliver therapeutics, offering a dual strategy for addressing the disease. In this study, fucoidans from <em>F. vesiculosus</em> and <em>U. pinnatifida</em> with two different molecular weights (<em>M</em><small>_W</small>) of each were initially screened for <em>in vitro</em> anti-angiogenic potential using the tube formation assay with HUVEC cells. The higher <em>M</em><small>_W</small> fucoidans, which represent native <em>M</em><small>_W</small> fucoidan, exhibited greater anti-angiogenic activity and were subsequently combined with 2,2-bis(hydroxymethyl)propionic acid (bis-MPA)-based dendrimers (generation 2) at different fucoidan/dendrimer (F/D) mass ratios to form self-assembled nanoparticles through electrostatic interactions. Optimisation yielded two nanoparticle types with positive (F/D = 1 : 2) and negative (F/D = 2 : 1) zeta potentials, which were characterised for their physicochemical properties, including hydrodynamic diameter, zeta potential, chemical composition (FTIR), and morphology (TEM). These nanoparticles presented a near-spherical shape, were cytocompatible, and did not cause haemolysis. Positively charged nanoparticles showed stronger anti-angiogenic activity than negatively charged ones. Since the dendrimers alone were also anti-angiogenic, the overall effect likely results from the combined contribution of both components, with nanoparticle assembly potentially playing a role. Overall, these findings highlight the potential of fucoidan/dendrimer nanoparticles as multifunctional platforms for cancer nanomedicine, by targeting angiogenesis and potentially serving as drug or gene delivery systems.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 574-584"},"PeriodicalIF":0.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00362h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558503","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":"Reformulating lumefantrine as Flash NanoPrecipitated particles and the impact of incorporation into milk-based formulations on drug solubilisation during digestion","authors":"Malinda Salim, Kurt D. Ristroph, Thomas Eason, Gisela Ramirez, Andrew J. Clulow, Robert K. Prud'homme and Ben J. Boyd","doi":"10.1039/D5PM00294J","DOIUrl":"https://doi.org/10.1039/D5PM00294J","url":null,"abstract":"<p >Lumefantrine and artemether are currently used as one of the first line therapies for treatment of uncomplicated malaria. However, commercially-available lumefantrine/artemether tablets often result in poor and variable oral bioavailability due to low aqueous solubility of the drugs. To circumvent these issues, consumption of food containing lipids with the lumefantrine/artemether tablet(s) is recommended to increase exposure of the drugs, which brings high variability to the systemic drug exposure. In this study, we investigated the potential use of infant formula as a milk-based lipid formulation to improve the solubilisation of lumefantrine/artemether with controlled fat content, both as a formulation for the two drug substances as well as when co-dosed with lumefantrine after re-formulation into nanoparticles. Time-resolved synchrotron small angle X-ray scattering (SAXS) was used to probe the solubilisation behaviour of the drugs and high-performance liquid chromatography (HPLC) was used to quantify the amount of drugs dissolved during digestion. Findings from these studies suggest that the solubility of artemether in undigested and digested infant formula was greater than 5 fold relative to lumefantrine and that 5 g of fat was not sufficient to completely solubilise a 120 mg lumefantrine dose. When formulated as nanoparticles, there was evidence of slight lumefantrine crystallisation when the highly amorphous drug powder was added to infant formula but digestion did not appear to significantly affect the presence of crystalline lumefantrine. These findings suggest a potential reduced food effect for lumefantrine nanoparticles compared to the crystalline counterpart, further highlighting that lumefantrine nanoparticles may be orally administered in both fasted and fed conditions.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 564-573"},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00294j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558502","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":"Rapid plasma membrane reorganisation and endocytosis in HER2 breast cancer cells incubated with trastuzumab decorated polymer nanoparticles","authors":"Carwyn S. Hughes, Saeed Tayeb, Duncan Muir, Anthony J. Hayes, Peter Watson and Arwyn T. Jones","doi":"10.1039/D5PM00168D","DOIUrl":"https://doi.org/10.1039/D5PM00168D","url":null,"abstract":"<p >Knowledge on HER2+ breast cancer biology has informed drug design leading to targeted therapies giving improved clinical outcomes. Drug resistance and disease relapse, however still drive a continuous need for more efficacious and reliable therapeutics. Nanoparticles (NPs) as HER2 targeting nanomedicines offer new hope for selective targeting of HER2 within and beyond solid tumours, together with concomitant delivery of therapeutic cargo. For initial preclinical characterisation, studies on NP endocytosis and drug delivery are often performed in HER2+ breast cancer cell models, but information on initial NP-HER2 dynamics at the plasma membrane and how this impacts endocytic uptake and delivery efficiency is largely missing. Here using polymer poly(lactic-<em>co</em>-glycolide) acid NPs decorated with different valencies of the HER2 targeting monoclonal antibody trastuzumab, we have designed approaches to immediately study the impact of NP-HER2 targeting on high and low HER2 expressing breast cancer cell models. Using resonant scanning confocal imaging of live cell plasma membrane dynamics, we show in very high detail and within 10 minutes of cell exposure of the receptor to the NPs, extensive blebbing and ruffling of the plasma membrane, manifesting before much longer uptake of the NPs into the cell interior. Plasma membrane reorganisation was rapidly reversible, with cells reaching baseline morphology in 30 minutes. Our findings were confirmed at the ultrastructural level by scanning electron microscopy in cells fixed within 10 and 30 minutes of exposure to the NPs. Endocytic traffic of the NPs was in part directed to lysosomes and we discover a relationship between antibody valency and the ability of the NPs to deliver the chemotherapeutic agent doxorubicin to mediate cell death. Knowledge gained from these studies offers new approaches to study NP-cell dynamics in different NP-receptor settings and how receptor targeting influences plasma membrane organisation, endocytosis and delivery.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 390-400"},"PeriodicalIF":0.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00168d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558603","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":"Lung physiologically based pharmacokinetic modelling to predict sublingual buprenorphine kinetics following oral inhalation","authors":"Tobechi Brendan Nnanna, Daniel Okwudili Nnamani, Elias Bestman Adikwu and Chisom Anthony Nnanna","doi":"10.1039/D5PM00266D","DOIUrl":"https://doi.org/10.1039/D5PM00266D","url":null,"abstract":"<p >The pulmonary system embodies a heterogeneous yet highly efficient interface for xenobiotic uptake, offering unique translational opportunities for pharmacokinetic modelling. The sublingual route is widely exploited to deliver buprenorphine, a lipophilic partial μ-opioid receptor agonist, while circumventing gastrointestinal degradation and hepatic first-pass metabolism; however, the pharmacokinetics of buprenorphine are marked by pronounced nonlinearity and variability driven by mucosal residence time, dissolution, and involuntary swallowing. In the absence of a native sublingual absorption module within the Open Systems Pharmacology (OSP) ecosystem, this study investigated whether a mechanistically constrained inhalation physiologically based pharmacokinetic (PBPK) framework could serve as a defensible surrogate to recover sublingual buprenorphine kinetics. A human inhalation PBPK model incorporating a 24-generation lung architecture was implemented in MoBi and PK-Sim, integrating morphometric and physiological descriptors with the physicochemical parameters of buprenorphine. Particle deposition was deliberately biased toward the extrathoracic and proximal tracheobronchial regions by selecting reported metered-dose inhaler particle sizes (MMAD ≈ 7.5 µm), thereby emulating sublingual mucosal exposure. The model explicitly resolved particle deposition, epithelial lining fluid dissolution, permeability-limited epithelial transfer, mucociliary clearance–driven swallowing, and systemic distribution, preserving the causal structure. Systemic disposition was described using a two-compartment model, with key parameters estimated through Monte Carlo optimisation. Model performance was evaluated against single-ascending-dose clinical data (2–24 mg) and further verified using independent studies of sublingual tablets and solutions. Across all dose levels (2–24 mg), predicted <em>C</em><small>_max</small> and AUC metrics were recovered within predefined two-fold acceptance limits, with prediction accuracies generally ranging from 73% to 138% for AUC and 81% to 103% for <em>C</em><small>_max</small>. The model robustly reproduced early exposure and peak timing while systematically underpredicting the terminal half-life, consistent with the structural constraints of the systemic disposition model and the absence of explicit mucosal depot or enterohepatic recirculation processes. Sensitivity analysis identified particle dissolution dynamics and mucociliary clearance kinetics as dominant drivers of exposure. In conclusion, this work demonstrates that an open-source inhalation PBPK framework can mechanistically and quantitatively approximate sublingual buprenorphine pharmacokinetics. The approach provides a transparent, extensible surrogate for sublingual absorption, supporting translational modelling and hypothesis generation when route-specific modules are unavailable.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 585-603"},"PeriodicalIF":0.0,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00266d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558504","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":"QbD product development: rapid optimization and scale-up of PBAE-based siRNA delivery via DoE-guided microfluidics","authors":"Adrian P. E. Kromer, Laetitia J. M. Eller, David C. Jürgens and Olivia M. Merkel","doi":"10.1039/D5PM00379B","DOIUrl":"10.1039/D5PM00379B","url":null,"abstract":"<p >Poly(β-amino ester) (PBAE)-based nanoparticles have emerged as promising carriers for RNA delivery, yet clear design rules linking formulation parameters to performance are still lacking. In this study, a Quality by Design (QbD)-guided and Design of Experiments (DoE)-driven approach was combined with high-throughput microfluidics to rapidly identify formulations with favorable physicochemical properties and consistent critical quality attributes (CQAs). Response Surface Modeling revealed that high total flow rates (TFR ≥ 10), nitrogen to phosphorus (N/P) ratios ≥10, and a Flow Rate Ratio (FRR) of 1 : 3 (buffer : ethanol) led to the formation of smaller, more stable particles. Among the polymers tested, a polymer candidate with a balanced composition of hydrophobic and hydrophilic side chains demonstrated optimal intraparticle stability and gene silencing performance. Notably, transfection efficiency depended strongly on formulation parameters beyond polymer type and N/P ratio, with flow rate ratio emerging as a key driver of gene knockdown kinetics. The lead formulation achieved ∼95% gene knockdown even after two weeks of storage at 4 °C. Scale-up production of the lead candidate confirmed the transferability of optimized Critical Process Parameters (CPPs) and preserved CQA profiles, validating the robustness of the design space. This study establishes a robust and scalable QbD-guided workflow for the development of microfluidically manufactured siRNA nanoparticles, enabling rapid optimization, reliable scale-up, and clinically relevant performance.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 379-389"},"PeriodicalIF":0.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286966","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":"A bioinspired, pH-responsive microsphere matrix of cold-water extracted Colocasia esculenta mucilage and alginate: a new approach for sustained oral delivery of tramadol","authors":"Shazia Noureen, Sobia Noreen, Fozia Batool, Shazia Akram Ghumman, Sara Hasan, Samina Aslam and Nisar Ahmed","doi":"10.1039/D5PM00263J","DOIUrl":"https://doi.org/10.1039/D5PM00263J","url":null,"abstract":"<p >Natural polymers derived from plant mucilages are increasingly explored as release-modifying agents in advanced drug delivery systems. This study presents an innovative approach utilizing cold-water extraction and ethanol precipitation to obtain <em>Colocasia esculenta</em> mucilage (CEM), which was then used to fabricate Tramadol hydrochloride-loaded microspheres <em>via</em> ionic gelation. A three-level, two-factor central composite design was employed to optimize a cross-linked CEM–alginate matrix, using polymer concentrations as independent variables, and particle size and encapsulation efficiency as response parameters. The optimized formulation exhibited stable, spherical microspheres with pH-responsive swelling and degradation behavior, high encapsulation efficiency (90.10%), and an average particle size of 726 μm. Characterization by FTIR, DSC, and XRD confirmed drug–polymer compatibility, while SEM analysis revealed a rough, wrinkled surface with fine pores. <em>In vitro</em> studies demonstrated pH-dependent drug release, achieving 67.30% release over 12 hours. <em>In vivo</em> evaluations in rabbits confirmed the formulation's safety, improved bioavailability, and prolonged gastrointestinal residence time. These results highlight the potential of cold-extracted CEM–alginate microspheres as a biocompatible, pH-responsive platform for sustained oral delivery of Tramadol. Furthermore, the simplicity and reproducibility of the ionic gelation method indicate good potential for formulation scalability, and future studies may explore the applicability of this CEM–alginate platform for other therapeutic agents requiring sustained oral delivery.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 423-440"},"PeriodicalIF":0.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00263j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558582","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":"Advanced mechanisms of polymer-based drug delivery systems for clinical applications","authors":"Barakat Olamide Ishola, Khandoker Asiqur Rahaman, Shaikh Abdur Razzak, Md Mahamudul Hasan Rumon, Md Salman Shakil and Shihab Uddin","doi":"10.1039/D5PM00242G","DOIUrl":"https://doi.org/10.1039/D5PM00242G","url":null,"abstract":"<p >Polymer-based drug delivery technologies have revolutionized modern therapeutics by enabling controlled, sustained, and targeted drug release. These systems employ diverse natural and synthetic polymers that engage with biological environments to exert therapeutic effects. The history of polymeric drug delivery systems, their classification, formulation techniques, mechanisms of action, and diverse applications across various disease conditions are essential for future advancements. Polymer chemistry has led to the development of stimuli-responsive polymers that release drugs in response to external triggers, such as pH, temperature, electricity, light, or ultrasound. Moreover, 3D printing technologies are increasingly employed to develop more complex, multifunctional, layered, polymer-based drug delivery systems. While polymer-based technologies have demonstrated remarkable potential in drug delivery, challenges like scalability, biocompatibility, and regulatory compliance persist. Interdisciplinary collaboration and multifaceted strategies can advance targeted treatments for life-threatening diseases and enhance quality of life through tissue regeneration.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 331-360"},"PeriodicalIF":0.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00242g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558600","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":"Self-nanoemulsifying drug delivery systems (SNEDDS) for treating neglected tropical diseases: affordable and scalable pathways for global health impact","authors":"João Paulo Figueiró Longo and Josué de Moraes","doi":"10.1039/D5PM00343A","DOIUrl":"https://doi.org/10.1039/D5PM00343A","url":null,"abstract":"<p >Nanomaterials present promising avenues for advancing global health, particularly in addressing neglected tropical diseases (NTDs). Affecting over a billion people, NTDs suffer from limited treatment options, often relying on drugs with poor solubility and bioavailability. This challenge is compounded by increasing drug resistance and difficulties in administering treatments effectively. This situation underscores a critical gap in pharmaceutical innovation, influenced more by market forces than by scientific limitations. The prohibitive costs and high failure rates of traditional drug development render standard innovation pathways economically impractical for neglected tropical diseases. Moreover, regulatory frameworks and intellectual property rights often hinder the development of affordable treatments for neglected tropical diseases. Nanotechnology, specifically self-nanoemulsifying drug delivery systems (SNEDDS), offers a scalable solution to overcome solubility and bioavailability barriers. By spontaneously forming emulsions in gastrointestinal fluids, SNEDDS eliminate complex manufacturing needs, as seen with successful clinical examples like ritonavir and cyclosporine. Leveraging these cost-effective, orally compatible platforms allows for the repurposing of existing drugs. Integrating such streamlined nanotechnologies into global health programs is essential to close the therapeutic gap in resource-limited settings.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 374-378"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00343a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558602","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":"Polymeric nano-in-microparticles for pulmonary delivery of remdesivir against SARS-CoV-2","authors":"Alison Tatiana Madrid Sani, Brenno da Cunha Lima, Beatriz Moreira Rodrigues, Michelle Alvares Sarcinelli, Marcelo Henrique da Cunha Chaves, Helvécio Vinícius Antunes Rocha, Natália Neto Pereira Cerize, Maria Helena Ambrosio Zanin, Juliana Terzi Maricato, Valker Araujo Feitosa and Carlota de Oliveira Rangel-Yagui","doi":"10.1039/D5PM00269A","DOIUrl":"https://doi.org/10.1039/D5PM00269A","url":null,"abstract":"<p >The COVID-19 pandemic underscored the urgent need for advanced drug delivery systems to enhance the safety and efficacy of existing antiviral therapies. This study presents an inhalable powder formulation of remdesivir (RDV) using polymeric nano-in-microparticles for pulmonary administration. RDV was nanoencapsulated in a polycaprolactone (PCL) matrix <em>via</em> emulsion–diffusion–solvent evaporation and stabilized with DPPC and Pluronic F127, resulting in nanoparticles (RDV-PCL-NP) of 184 ± 11 nm and 87% encapsulation efficiency. Cytotoxicity assays in Vero E6 cells confirmed the RDV-PCL-NP safety at therapeutic concentrations, with a marked reduction in the SARS-CoV-2 viral load at 5 µM RDV. The nanoparticles were spray dried with lactose, yielding a dry powder (RDV-PCL-MP) with 63% process yield. Physicochemical characterization (SEM, FTIR, DRX, DSC/TGA, laser diffraction) confirmed uniform particle size and stability (1–5 µm) of the RDV-PCL-MP inhalable powder. <em>In vitro</em> lung deposition studies showed 40% fine fraction and 39% respirable fraction. These findings support the potential of RDV-loaded nano-in-microparticles as a scalable pulmonary delivery platform to improve COVID-19 treatment.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 2","pages":" 552-563"},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2026/pm/d5pm00269a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147558535","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}