RSC Pharmaceutics最新文献

{"title":"Predicting absorption of compounds from an in vivo liver surface based on molecular weight or in vitro release using a dialysis membrane in combination with lipophilicity†","authors":"Fei Yuan, Ayaka Torigoe, Nao Mitsudome, Hirotaka Miyamoto, Shintaro Fumoto, Akira Toriba and Koyo Nishida","doi":"10.1039/D5PM00054H","DOIUrl":"https://doi.org/10.1039/D5PM00054H","url":null,"abstract":"<p >A liver surface application (LSA) was developed to reduce the side effects of chemotherapy in liver cancer. The effects of molecular weight (MW) and lipophilicity (log PC) on the absorption of hydrophilic and lipophilic compounds from the rat liver surface were examined. However, how these two factors simultaneously affect compound absorption remains unclear. The combined effects of MW and log PC on the absorption of these compounds in rats and mice were investigated. The compounds were administered to the liver surface using a cylindrical diffusion cell, and <em>in vitro</em> release experiments were conducted using a dialysis membrane to explore the relationship between release and absorption. The results indicate that log (PC/MW<small>^0.5</small>) has a significant linear correlation with log <em>P</em><small>_{app, absorption}</small> (<em>P</em><small>_app</small>, apparent permeability coefficient). Similarly, a significant correlation was observed between log (PC × <em>P</em><small>_{app, release}</small>) and log <em>P</em><small>_{app, absorption}</small>. These two relationships observed in rats were used to predict compound absorption in mice, and the predicted values closely matched the experimental data. This implies that both combinations of MW and <em>in vitro</em> release with log PC can explain compound absorption from the liver surface. This study provided important information for understanding the absorption characteristics of LSA.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 761-771"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00054h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624151","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":"Biomimetic nanoparticles for targeted therapy of liver disease","authors":"Veena Vijayan, Janitha M. Unagolla, Dhruvisha Panchal, Judith Eloyi John, Siddharth S. Menon and Jyothi U. Menon","doi":"10.1039/D5PM00044K","DOIUrl":"10.1039/D5PM00044K","url":null,"abstract":"<p >Liver fibrosis is a progressive and fatal condition characterized by stiffness and scarring of the liver due to excessive buildup of extracellular matrix (ECM) proteins. If left untreated, it can progress to liver cirrhosis and hepatocellular carcinoma (HCC)–one of the fastest-rising causes of cancer mortality in the United States. Despite the increased prevalence of liver fibrosis due to infections, exposure to toxins, and unhealthy lifestyles, there are no effective treatments available. Recent advances in nanomedicine can lead to more targeted and effective strategies for treating liver diseases than existing treatments. In particular, the use of biomimetic nanoparticles (NPs) such as liposomes and cell-membrane-coated NPs is of interest. NPs functionalized with cell membranes mimic the properties of the source cell used and provide inherent immune evasion ability, homologous adhesion, and prolonged circulation. This review explores the types of biomimetic coatings, different cargoes delivered through biomimetic NPs for various treatment modalities, and the type of core NPs used for targeting liver fibrosis and HCC.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 667-682"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056765","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":"Effect of shape on cellular internalization and anti-cancer efficacy of hydroxyapatite nanoparticles in an osteosarcoma cell line†","authors":"Simmi Gupta, Esha S. Attar, Vishvesh Joshi and Padma V. Devarajan","doi":"10.1039/D5PM00005J","DOIUrl":"https://doi.org/10.1039/D5PM00005J","url":null,"abstract":"<p >Hydroxyapatite nanoparticles (HAP NPs) with distinct morphologies were synthesized by the wet precipitation method by varying pH, and their shape was confirmed by scanning electron microscopy as spherical (pH 12), rod-like (pH 9), and needle-like (pH 8). The particle sizes of HAP NPs were 96.86 ± 1.48 nm for needle-shaped, 118 ± 4.32 nm for rod-shaped, and 94.43 ± 1.02 nm for spherical-shaped particles. XRD analysis showed clear and distinct peaks indicating crystalline nature, while FTIR confirmed the characteristic features of hydroxyapatite. The negative zeta potential of the HAP NPs was attributed to the presence of surface phosphate ions. The influence of HAP NP shape and size on intracellular uptake was evaluated in the MG-63 osteosarcoma cell line by Confocal Laser Scanning Microscopy (CLSM). CLSM results demonstrated that rod-shaped HAP NPs predominantly localized within the lysosome and nucleus, while spherical HAP NPs accumulated at the cell membrane. The MTT, clonogenic survival, cell scratch and transwell migration assays revealed that rod-shaped HAP NPs exhibited superior anticancer activity compared to their needle- and spherical-shaped counterparts and completely suppressed the clonogenic survival of MG-63 cells. Our findings confirm that the shape of HAP NPs is a critical factor influencing their intracellular uptake and anticancer activity.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 5","pages":" 1087-1095"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00005j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073542","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 molecular simulation-based deep neural network model for deciphering the adsorption of 5-Fluorouracil in COFs†","authors":"Khushboo Yadava and Ashutosh Yadav","doi":"10.1039/D5PM00007F","DOIUrl":"https://doi.org/10.1039/D5PM00007F","url":null,"abstract":"<p >A database of 1242 experimentally synthesized COFs has been studied to understand their potential as drug carriers by employing molecular simulations and machine learning models to analyze the adsorption abilities and predict the capacity of loading the anticancer drug, 5-fluorouracil. Our findings indicate that different organic linkers, structural features, binding sites, topologies, <em>etc.</em> of COFs play an important role in determining the maximum loading capacity and release parameters of 5-FU. The implementation of molecular simulations-based machine learning methods for drug adsorption studies in COFs is rare in the literature. Once the model was validated, we studied the maximum loading capacity of 5-FU in a series of COFs, 102–108 and 112, from the COF database, as these exhibited a gradual trend in textural properties, aiming to understand this trend and the correlation between their structure and loading capacity. Then, we proceeded to study the adsorption process in detail in 4 of the COFs: three 2D COFs—COF-206, <em>i.e.</em>, D<small>_CuPc</small>–A<small>_NDI</small>-COF; COF-362, <em>i.e.</em>, PI-COF-3; and COF-398, <em>i.e.</em>, Py-DBA-COF-1—and one 3D COF—COF-363, <em>i.e.</em>, PI-COF-4. Radial distribution function and adsorption energy analyses revealed some important interactions and thermodynamic parameters leading to strong binding and slow release of 5-FU. The adsorption energy values in the top-performing COFs fall within the range of −8.43 to −42.25 × 10<small>³</small> kJ mol<small>⁻¹</small>. The correlation of ML input parameters in terms of various chemical and structural descriptors with the maximum loading capacity is discussed. From the molecular simulations, COF-362 is the best-performing COF in terms of loading capacity and adsorption energy values. The ML models, <em>i.e.</em>, random forest, decision tree and three deep neural networks, were trained on 80% of the total data, while the remaining 20% of the data was used to test the models. DNN model-3 was chosen as the final model for further analysis based on <em>R</em><small>²</small> = 0.87, RMSE = 189.81, and MAE = 100.87. SHapley Additive exPlanations (SHAP) analysis and the feature importance chart indicated that among the structural descriptors, <em>S</em><small>_acc</small>, LCD, and <em>V</em><small>_f</small>, and among the chemical descriptors, C, H, and N, had the most positive impact on the output predictions of the model. Finally, a graphical user interface based on the best-performing ML model was created to predict the 5-FU loading capacity of COFs. This will save users time without the need to run the code or perform various tedious drug-loading experiments.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 703-717"},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00007f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624148","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":"Comparative hygroscopic aerosol particle sizing measurements of the hygroscopic growth of inhaled pharmaceutical ingredients†","authors":"Yiliang Lance Jiang, Josef Kadziola, Jose R. Ruiz, Richard Friend and Jonathan P. Reid","doi":"10.1039/D4PM00310A","DOIUrl":"https://doi.org/10.1039/D4PM00310A","url":null,"abstract":"<p >The size distribution of an inhaled pharmaceutical aerosol generated by a nebulizer is a critical parameter influencing the deposition and therapeutic effect of the medication. Relative humidity (RH) can alter size distribution by promoting particle growth through condensation, depending on the hygroscopicity of the formulation. In this study, we evaluate the effect of RH on mannitol, trehalose, salbutamol, and tobramycin aerosols using the Comparative Hygroscopic Aerosol Particle Sizing (CHAPS) technique under varying RH conditions, ranging from ambient to physiological levels. The results demonstrate that RH significantly influences the aerosol particle size, with particle growth becoming more pronounced as RH exceeds 95%. The findings confirm that understanding the relationship between geometric radial growth factors (rGFs) from single droplet size measurements and the aerodynamic rGF is essential for more accurate prediction of plume size distribution, especially at lower RH levels. We also demonstrate consistency between the size distributions measured by CHAPS and a Next Generation Impactor (NGI), with CHAPS providing higher resolution in size and time and data on actuation-by-actuation variability in size distribution and aerosol dose.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 630-643"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00310a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100161","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":"Sometimes less is more: avidity-dependent transport of targeted polymersomes across the blood–brain-barrier†","authors":"Ana Alves, Peter Pfeifer, Andreia Marinho, Claúdia Nunes, Salette Reis, Domingos Ferreira, Marta Correia-da-Silva, Paulo C. Costa, Giuseppe Battaglia, Íris L. Batalha and Cátia D. F. Lopes","doi":"10.1039/D4PM00338A","DOIUrl":"https://doi.org/10.1039/D4PM00338A","url":null,"abstract":"<p >Over the past decade, roughly 10% of new FDA-approved drugs targeted central nervous system (CNS) disorders, while it has been estimated that 98% of small-molecule drugs and nearly all large-molecule therapeutics are unable to cross the blood–brain barrier (BBB). There is a clear need for novel therapeutic modalities that promote receptor-mediated transcytosis modulation and efficiently deliver drugs to the brain. Here, we show that poly(ethylene glycol)-<em>b</em>-poly(lactic acid) (PEG-<em>b</em>-PLA) polymersomes functionalised with a transferrin receptor (TfR)-targeted peptide can effectively deliver a glioblastoma small drug therapeutic (3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone; XGAc) through a two-dimensional model of the BBB and that the transport is dependent on the avidity of the nanoformulation. By adjusting the density of targeting peptides on polymersomes, we present a novel strategy to enhance the efficiency of BBB receptor-mediated transcytosis. These findings highlight the promise of precision-tuned polymersomes in overcoming the BBB and advancing treatments for glioblastoma and other brain diseases.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 535-540"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00338a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100115","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":"Vaccine formulation design: challenges and opportunities","authors":"Saman Zafar, Ambreen Akhtar, Elshaimaa Sayed, Ekhoerose Onaiwu, Muhammad Sohail Arshad and Zeeshan Ahmad","doi":"10.1039/D5PM00017C","DOIUrl":"https://doi.org/10.1039/D5PM00017C","url":null,"abstract":"<p >The rise in activity and multi-faceted impact of infectious agents such as human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented increase in morbidity and mortality around the globe. The spread of infectious diseases at an alarming rate has led to accelerated research on vaccine therapeutics, which can be further exemplified with COVID (coronavirus disease) vaccine development as a global emergency. This review aims to provide insights into vaccine development, components, manufacturing processes, types/platforms and strategies to improve their efficacy. The development of vaccines comprises four stages: (1) exploratory and preclinical, (2) clinical, (3) approval and (4) manufacturing and post-marketing surveillance. Vaccine formulations comprise antigens, adjuvants, preservatives, stabilizers, antibiotics, diluents and trace components. Vaccine manufacturing is a multi-step process involving antigen generation, release, purification, addition of other ingredients (<em>e.g.</em>, adjuvants, preservatives, stabilizers, <em>etc</em>.), quality control testing and filling. Conventional vaccine platforms include live attenuated, inactivated/killed, toxoid, polysaccharide and polysaccharide conjugate, synthetic peptide and virus-like particles. Advanced technologies include viral vectors, bacterial vectors, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) vaccines. These platforms provide rapid development of vaccines at a relatively low cost compared to conventional counterparts. Several approaches have been adopted for improving vaccine efficacy such as the inclusion of adjuvants and delivery of vaccines <em>via</em> mucosal and transcutaneous routes. Efficient uptake of vaccine antigens by microfold cells (found in the epithelium covering mucosa-associated lymphoid tissues) with subsequent transfer to the underlying antigen-presenting cells provides an efficient vaccine delivery route. In the case of the transcutaneous route, abundant antigen presenting cells found in the skin layer (<em>e.g.</em>, Langerhans) ensure efficient vaccine delivery and induction of potent immune responses. Additionally, both these routes can overcome limitations associated with traditionally employed parenteral routes, such as risk of disease transmission in unhygienic conditions and reuse of contaminated needles, production of biohazardous waste, requirement of trained personnel for administration, invasiveness and poor patient compliance. Identification of conserved pathogenic sequences using advanced genetic engineering methods, machine learning, and artificial intelligence can help in developing efficient vaccines. Moreover, global partnerships, funding and provision of resources from the World Health Organization (WHO) can ensure vaccine development, testing and research activities for developing countries.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 490-516"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00017c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100114","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":"Exploiting nano-in-micro-technologies to couple PLGA-hydroxyl-FK866 nanoparticles to a hydrogel network for local drug release†","authors":"Eugenia Spessot, Xue Bai, Daniel Moranduzzo, Chen Zhao, Sam Butterworth, Devid Maniglio and Annalisa Tirella","doi":"10.1039/D4PM00334A","DOIUrl":"https://doi.org/10.1039/D4PM00334A","url":null,"abstract":"<p >Technological advancements in the formulation and delivery strategies of potent chemotherapeutic agents have been exploited to direct a site-specific drug delivery for the local treatment of tumours. Of these, new generations of nanoparticles are engineered to control the release of therapeutic agents, but they still possess off-target and overall systemic delivery. Injectable hydrogels have unique physico-chemical properties enabling their use as carriers to ensure site-specific targeting. Based on such observations, nanoparticle-loaded hydrogels represent an optimal candidate to both make use of controlled release chemotherapeutic agents (nanoparticles) and local delivery agents (hydrogels) using minimally invasive procedures to reach the target site. Here, we explore the interaction of drug-polymer conjugated nanoparticles with an alginate-based hydrogel network to confine and release a highly cytotoxic compound (hydroxyl-FK866). Specifically, chitosan coating was used to covalently link poly(lactic-<em>co</em>-glycolic acid) nanoparticles to oxidised alginate: confinement and interaction of nanoparticles within alginate-based hydrogels were evaluated using atomic force microscopy measurements, confirming the nanoparticle/hydrogel interaction. Deployment of composite injectable hydrogels in 3D printing was finally investigated. Rheological characterisation and printability tests were performed to assess the printability of alginate-based drug delivery systems to match site-specific geometrical requirements. Then, alginate hydrogels loaded with nanoparticles were ionically crosslinked to match the properties of soft tissues (<em>e.g.</em> breast tissue). The efficacy of 3D printed hydrogels loaded with a known dose of hydroxyl-FK866 was tested using human breast cancer MDA-MB-231 cells. Results confirmed the expected cytotoxicity, showing approx. 52% toxicity of the hydrogel loaded, after 48 hours of incubation, whereas lower viability (approx. 36%) was measured in cells treated with free nanoparticles (control).</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 4","pages":" 718-730"},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00334a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624149","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":"Development of solid drug nanoparticle dispersions for pulmonary delivery of niclosamide and nitazoxanide via vibrating mesh nebulisation†","authors":"Catherine Unsworth, Andrew B. Dwyer, Alison C. Savage, James J. Hobson, Jonathan Massam, Tom O. McDonald, Paul Curley, Andrew Owen, Andrew O'Sullivan, Ronan MacLoughlin and Steve P. Rannard","doi":"10.1039/D5PM00006H","DOIUrl":"https://doi.org/10.1039/D5PM00006H","url":null,"abstract":"<p >The optimum delivery of very poorly soluble drug compounds is challenging, especially if targeting of disease sites is required. Delivery to the lung is hampered by a range of physiological issues, and inhalation may be the most appropriate route. When breathing is compromised by infection or poor lung capacity, nebulisation may enable therapeutics to be carried deep into the respiratory tract. Here we report the development of nebulised aqueous formulations of two highly water-insoluble drugs with demonstrated anti-SARS-CoV-2 activity and evaluate their pulmonary delivery using <em>in vitro</em> models that include the breathing patterns of children and COVID-19 infected adults.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 517-526"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d5pm00006h?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100113","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":"Redox-responsive micellar-like nanoparticles can overcome intrinsic multi-drug resistance in tumour spheroids of triple negative breast cancer†","authors":"Cíntia J. Monteiro, Patrícia F. Monteiro, Alessandra Travanut, Muhammad Gulfam, David M. Heery, Anna Grabowska and Cameron Alexander","doi":"10.1039/D4PM00336E","DOIUrl":"https://doi.org/10.1039/D4PM00336E","url":null,"abstract":"<p >Triple negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat, due to its aggressiveness, high heterogeneity and lack of targeted therapies. Efforts have been made to elucidate the mechanisms by which TNBC cells become drug-resistant, aiming to identify new molecular targets for the development of effective treatments. Here, we have generated a TNBC 3D multi-cellular spheroid model using MDA-MB-231 cells and assessed the efficacy of drug delivery formulations based on docetaxel (DTX)-loaded micellar-like nanoparticles (MLNP) compared with free DTX. We assessed the viability and the induction of apoptosis in the treated spheroids using established apoptosis and necrosis biomarkers: annexin-V, PI, Sytox and caspase 3 and 7 activity by flow cytometry. Given the efficacy results of the MLNPs and free DTX, the expression of selected genes related to resistance in breast cancer cells was assessed by RT-qPCR (real-time polymerase chain reaction) as well as western blot and immunofluorescence of the drug resistance protein (ABCG2/BCRP) in both 3D and 2D cell culture models of MDA-MB-231 cells. The results from these assays indicate that the TNBC 3D multi-cellular spheroids exhibit an intrinsic multi-drug resistance (MDR) through the up-regulation of ABCG2/BCRP gene and protein, compared to monolayers of the same cell line. Moreover, the results also demonstrate that the MLNPs had the best efficacy against TNBC 3D spheroids whereas the free drug was less efficacious. This suggests that the MLNPs were able to overcome the MDR of the TNBC 3D cell culture model when compared to free DTX.</p>","PeriodicalId":101141,"journal":{"name":"RSC Pharmaceutics","volume":" 3","pages":" 644-656"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/pm/d4pm00336e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100162","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}