European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Elucidating structure of endogenous phospholipids on in vivo absorption of octreotide following lung administration","authors":"Lu Qin ,&nbsp;Qiyao Zhai ,&nbsp;Zhixiang Cui ,&nbsp;Hongfang Li ,&nbsp;Jian Guan ,&nbsp;Ziwei Zhang ,&nbsp;Enyu Xu ,&nbsp;Xin Zhang ,&nbsp;Shirui Mao","doi":"10.1016/j.ejpb.2025.114706","DOIUrl":"10.1016/j.ejpb.2025.114706","url":null,"abstract":"<div><div>Phospholipids as endogenous pulmonary components have received extensive attention on promoting the transmembrane absorption of peptides and proteins. However, considering their diversified structure, influence of phospholipid structural characteristics on drug absorption across lung epithelial cells, together with the underlying absorption-promoting mechanisms, remain unclear. Therefore, in this study, taking octreotide as a model drug, phospholipids with different “tail” and “head” structures were adopted in the form of blank liposomes to investigate their structural characteristics on drug absorption utilizing both 3D Transwell cell models and Sprague Dawley rats. It was demonstrated that indeed the absorption-enhancing capacity of phospholipids was their structure-dependent. Among the tail (non-polar) structures, a moderately increased alkyl chain length could facilitate drug absorption across the pulmonary epithelium, with the highest enhancement ratio observed for Dipalmitoyl Phosphatidylcholine (DPPC) containing a palmitoyl group of 16 carbons, and its apparent permeability coefficient (<em>P_app</em>) increased 2.4 times compared to octreotide solution. Among the head (polar) structures, charged functional groups could contribute to better drug permeation, and Dipalmitoyl Phosphatidylserine (DPPS) containing a protonated amino (<img>NH₃⁺) and a deprotonated carboxyl (<img>COO^-) exhibited a 4.6-fold increase in <em>P_app</em> compared to octreotide solution. Mechanism studies disclosed a paracellular pathway-mediated drug transport across lung epithelial cells. In summary, phospholipids can serve as biosafe absorption enhancers for pulmonary drug delivery, with the extent depending on their structure, which could provide a theoretical basis for pulmonary delivery of macromolecules for systemic absorption.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114706"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and characterization of a multifunctional hyaluronic acid-based microneedle system for diabetic wound healing","authors":"Jianmin Chen ,&nbsp;Wenqin Zhang ,&nbsp;Xinyi Zhang ,&nbsp;Yuelian Zhang ,&nbsp;Guozhong Yang ,&nbsp;Dechao Yang ,&nbsp;Yunhua Gao","doi":"10.1016/j.ejpb.2025.114704","DOIUrl":"10.1016/j.ejpb.2025.114704","url":null,"abstract":"<div><div>Diabetes mellitus (DM)-associated wounds, characterized by chronic bacterial infections and elevated glucose levels, present significant challenges to effective healing. To overcome these issues, a novel transdermal drug delivery system was developed, integrating microneedles (MNs) with biofilm-penetrating capability, the wound-healing properties of hyaluronic acid (HA), the antibacterial effects of silver nanoparticles (AgNPs), and the glucose-lowering action of insulin (Ins). Named HAMNs@AgNPs-Ins, this system demonstrated optimal morphological characteristics, robust mechanical strength, and 100 % skin penetration efficiency. It exhibited sustained antibacterial activity <em>in vitro</em>, ensured skin safety, and provided controlled, steady blood glucose reductions, achieving a 72.29 % reduction at 8 h, compared to the sharp decline seen with subcutaneous injection. Additionally, wound healing experiments showed a significant improvement in the healing rate of 89.66 ± 1.34 % in the HAMNs@AgNPs-Ins group, compared to 48.19 ± 9.03 % in the control group. These results underscore the potential of HAMNs@AgNPs-Ins as an effective treatment for DM-associated wounds.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114704"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravitreal CBD-loaded niosomes enhance retinal neuroprotection in ischemic injury","authors":"Carolina Nunes Silva ,&nbsp;Lays Fernanda Nunes Dourado ,&nbsp;Bárbara Leão Agata ,&nbsp;Maísa Angélica Silva Fernandes ,&nbsp;Marina França Dias ,&nbsp;Sílvia Ligorio Fialho","doi":"10.1016/j.ejpb.2025.114705","DOIUrl":"10.1016/j.ejpb.2025.114705","url":null,"abstract":"<div><div>Cannabidiol (CBD) has emerged as a promising treatment for conditions like retinal ischemia, characterized by reduced blood flow to the retina and significant vision loss. Despite its therapeutic potential, CBD’s clinical application could be limited by due to its low bioavailability. This study investigates the efficacy of CBD-loaded niosomes as a neuroprotective formulation for the use in ocular therapies related to retinal ischemia. We investigated the neuroprotective effects of CBD using a nanodispersed system (niosomes) administered via intravitreal injection in rats’ eyes. Niosomes underwent characterization for size, distribution, zeta potential, morphology, and encapsulation efficiency. Safety and neuroprotective activity were assessed by electroretinography (ERG), confocal and transmission microscopy and histology. Niosomes exhibited nanometric size (100–400 nm) and stability, showing good tolerance in animals. ERG results demonstrated higher b-wave amplitudes in animals pre-treated with niosomes + CBD compared to the control group following ischemic injury induced by a sudden increase in IOP. Histological and confocal microscopy analyses of retinas from the niosomes + CBD group showed preserved structure compared to the ischemic control group, suggesting significant retinal protection by intravitreally injected niosomes + CBD before ischemia. CBD-loaded niosomes effectively preserved retinal function, highlighting the neuroprotective potential of CBD against retinal ischemia. This formulation presents a promising and innovative treatment for ischemic retinal diseases.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114705"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability of Jurkat cells during short-term liquid storage analyzed by flow imaging microscopy","authors":"Alexandra Roesch ,&nbsp;Cornelia Hiemenz ,&nbsp;Teresa Findley ,&nbsp;Ilya Goldberg ,&nbsp;Roland Windisch ,&nbsp;Christian Wichmann ,&nbsp;Gideon Kersten ,&nbsp;Tim Menzen","doi":"10.1016/j.ejpb.2025.114703","DOIUrl":"10.1016/j.ejpb.2025.114703","url":null,"abstract":"<div><div>The viability of cell-based medicinal products (CBMPs) is a critical quality attribute and must be assessed throughout the product lifecycle to contribute to a safe and potent drug product. In this study, we investigated the impact of short-term liquid storage conditions, encountered during manufacturing of CBMPs, such as holding times outside cell culture conditions and medium composition, on cell viability.</div><div>As a model for T cells Jurkat cells were used and stored in different storage media for up to 24 h outside a freezer and outside of cell culture conditions. The effect of storage in different storage media, i.e., cell culture medium or phosphate buffered saline (PBS), dimethyl sulfoxide (DMSO) at different storage temperatures as well as the impact of pH on the cell viability was assessed. The viability of the cells was assessed by (i) flow cytometry with an Annexin V and CalceinAM staining or (ii) machine learning tools, leveraging the morphological information of flow imaging microscopy images. Cell images obtained by flow imaging microscopy were analyzed with both the ParticleSentry^AI imaging software and a convolutional neural network (CNN) for fast and semi-automated viability assessment.</div><div>Throughout storage conditions similar to those during processing of CBMPs, a decrease in cell viability was observed over time for all conditions based on Annexin V and CalceinAM staining. Additionally, we observed a damaging effect of DMSO over time, whereas this effect was more pronounced at room temperature compared to refrigerated temperatures. The ParticleSentry^AI software was useful to detect qualitative differences in the cell viability as a shift towards non-viable cells could be observed throughout storage based on flow imaging microscopy images without prior sample preparation. Viability determination based on the CNN underestimated cell viability when compared to the flow cytometry assays, however the same trends were determined.</div><div>In summary, non-frozen storage of CBMPs should be kept to a minimum. However, standing times throughout the manufacturing of CBMPs as well as during in-use cannot be completely avoided and therefore, the optimal storage conditions have to be carefully evaluated. Additionally, further analytical development is needed to implement machine learning tools suitable for reliable viability quantification without additional sample preparation such as staining.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114703"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaginal formulation development: A strategy based on aptamer-guided liposome for human papillomavirus-induced lesions","authors":"Jéssica Lopes-Nunes ,&nbsp;Melanie Lopes ,&nbsp;Beatriz Rosado ,&nbsp;Izamara Gomes Maocha ,&nbsp;Joana Rolo ,&nbsp;Carlos Gaspar ,&nbsp;Bruno Pires ,&nbsp;Tiago Rosado ,&nbsp;Eugénia Gallardo ,&nbsp;Ana Palmeira-de-Oliveira ,&nbsp;José Martinez-de-Oliveira ,&nbsp;Catarina Ferreira ,&nbsp;Maria Paula Cabral Campello ,&nbsp;António Paulo ,&nbsp;Beatriz Medeiros-Fonseca ,&nbsp;Luís Félix ,&nbsp;Carlos Venâncio ,&nbsp;Maria de Lurdes Pinto ,&nbsp;Paula A. Oliveira ,&nbsp;Rita Palmeira-de-Oliveira ,&nbsp;Carla Cruz","doi":"10.1016/j.ejpb.2025.114693","DOIUrl":"10.1016/j.ejpb.2025.114693","url":null,"abstract":"<div><div>Human Papillomavirus (HPV) is the main cause of cervical cancer, and formulations have been widely used to treat vaginal lesions caused by HPV.</div><div>Herein, liposomes with acridine orange derivative C₈ were produced and functionalized with AT11 aptamer. Subsequently, they were incorporated into a formulation, prepared based on the universal placebo formulation, which included <em>Thymus vulgaris</em> (TEO) or <em>Origanum vulgare</em> (OEO) essential oils. The formulation was technologically characterized and permeation of C₈ into vaginal tissue was determined. To assess its biological effect, cell viability and internalization tests were carried out using the MTT assay and confocal microscopy, respectively, and antimicrobial susceptibility was also assessed. The prepared formulations were able to internalize cells and reduce cell viability, especially in cancer cell lines. Additionally, formulations showed promising antibacterial and antifungal effects. The effect of the formulation containing TEO and the C₈ AT11 liposomes was also tested <em>in vivo</em> in HPV16 transgenic and wild type mice. Briefly, the formulation proved to be safe for animals and presented some therapeutic potential, namely through the reduction of ear epithelial cells’ proliferation. Overall, results suggest that essential oils can increase the anticancer potential of liposomes with associated C₈ and AT11 promotes their selectivity towards cancer cells.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114693"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlled release of deferiprone using iron-responsive nanoparticles integrated with dissolving microneedle for novel alternative treatments of β-thalassemia major","authors":"Muh.Taufik Hidayat ,&nbsp;Sitti Nur Khadijah Maharani ,&nbsp;Indianty Dwi Ramadhany ,&nbsp;Nur Izzah Khairani ,&nbsp;Nur Annisa Rahman ,&nbsp;Andi Dian Permana","doi":"10.1016/j.ejpb.2025.114702","DOIUrl":"10.1016/j.ejpb.2025.114702","url":null,"abstract":"<div><div>Iron chelating agents (ICs) such as conventional deferiprone are often ineffective when exposed to normal conditions due to their uncontrolled release when treating iron overload in ß-thalassemia major (ß-TM) due to the effects of blood transfusion. Iron deficiency and gastrointestinal side effects are crucial problems that can occur. Therefore, DFP was prepared as nanoparticles (NPs) coated with an iron-responsive (IR) polymer with an average particle size of 354.70 ± 10 nm to control its release. To facilitate optimal delivery, NP-IR-DFP was integrated into a dissolving microneedle (DMN) fabricated with biodegradable and biocompatible poly(vinylpyrrolidone) and poly(vinyl alcohol) polymers. The results showed that the NP-IR-DMN provided excellent insertion and mechanical strength and dissolved quickly after application. In vitro and <em>ex-vivo</em> studies revealed the more controllable release of NP-IR-DFP after integration with the DMN (NP-IR-DMN) for up to 24 h. Most importantly, the developed formula was hemocompatible and did not irritate the skin or cause tissue damage. Furthermore, the <em>in vivo</em> pharmacokinetics were further investigated for 24 h, which revealed short concentration (C_max of 0.07 ± 0.03 μg/mL) and t_1/2 (3.66 ± 0.76 h) under normal conditions and long-term iron overload-modeling conditions with C_max (2.90 ± 0.14 μg/mL) and t_1/2 (10.13 ± 1.00 h). This approach can extend beyond oral delivery by controlling the release of DFP, which can only be released in conditions of iron overload, and has the potential to prevent iron deficiency and excess, thus increasing the efficacy of DFP in β-TM therapy.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114702"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modern strategy for digital real-time release testing in continuous tablet manufacturing","authors":"Selma Celikovic ,&nbsp;Jakob Rehrl ,&nbsp;Rúben Martins Fraga ,&nbsp;Martin Steinberger ,&nbsp;Johannes Khinast ,&nbsp;Martin Horn ,&nbsp;Stephan Sacher","doi":"10.1016/j.ejpb.2025.114700","DOIUrl":"10.1016/j.ejpb.2025.114700","url":null,"abstract":"<div><div>The pharmaceutical industry is currently moving away from traditional approaches to quality control with off-line quality tests, limited in-line process monitoring and minimal control strategies towards more sophisticated methods. This transition addresses several critical aspects, including the reduction of ecological and economic footprints and ensuring the safety for patients and personnel. In that context, the initial step is the application of process monitoring tools, such as process analytical technology (PAT) and soft sensors, for real-time product quality assessment. This will enable real-time release testing (RTRT), which redefines conventional approaches by relying solely on the process data reported by equipment or collected from sensors to predict the product quality. However, the implementation of RTRT requires reliable material tracking algorithms, which align the process data with the product’s characteristics.</div><div>This study proposes a modern digital RTRT strategy that aligns process data collected from a state-of-the-art manufacturing line with a sophisticated process monitoring strategy for specific product quantities, i.e., single dosage units (tablets). To trace the material through the production line and align it to the collected process data, residence time distribution (RTD) models and material tracking algorithms were developed. The digital RTRT strategy was designed and demonstrated using the industrial manufacturing line ConsiGma^TM-25. The developed strategy makes full product quality information digitally available, including critical quality attributes (CQAs) and processing conditions experienced during the production. The obtained results were validated using traditionally established off-line methods.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114700"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-dispersible eutectic mixtures with fenofibrate and ibuprofen: Processability and API particle size","authors":"Peter Schlosser,&nbsp;Heike Bunjes","doi":"10.1016/j.ejpb.2025.114701","DOIUrl":"10.1016/j.ejpb.2025.114701","url":null,"abstract":"<div><div>In order to increase the dissolution rate of poorly water-soluble drugs, the preparation of eutectics is a practical way to minimize the drug particle size without the need of grinding and handling of poorly flowing powders. The use of solid self-dispersible excipients as a component of the eutectic may further enhance the drug dissolution rate. In the current study, phase diagrams of eutectic mixtures of polyethylene glycol stearates and polyethylene glycol stearyl ethers differing in their polyethylene glycol chain lengths and two model drugs were established. Their processability and disintegration properties were investigated. Moreover, the resulting drug particle sizes in the eutectics were determined. The eutectic concentration and temperature of fusion of the eutectics increased with the melting temperature of the respective excipient. The eutectics with the self-dispersing excipients disintegrated faster than more conventional eutectics containing polyethylene glycols that were prepared for comparison. The drug particle sizes were smaller for mixtures with higher recrystallization tendency and with drug concentrations close to the eutectic concentration.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114701"},"PeriodicalIF":4.4,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Starch-Based scaffold produced by FDM 3D printing technique as Innovative and biosustainable wound dressing","authors":"Franco Dominici ,&nbsp;Anna Imbriano ,&nbsp;Debora Puglia ,&nbsp;Cinzia Pagano ,&nbsp;Francesca Luzi ,&nbsp;Aurora Rafanelli ,&nbsp;Alessandro Di Michele ,&nbsp;Francesco Bonacci ,&nbsp;Maria Rachele Ceccarini ,&nbsp;Sara Primavilla ,&nbsp;Andrea Valiani ,&nbsp;Leonardo Tensi ,&nbsp;Carmen Laura Pérez Gutierrez ,&nbsp;Raquel De Melo Barbosa ,&nbsp;César Viseras ,&nbsp;Maurizio Ricci ,&nbsp;Luana Perioli","doi":"10.1016/j.ejpb.2025.114698","DOIUrl":"10.1016/j.ejpb.2025.114698","url":null,"abstract":"<div><div>Starch is a safe biopolymer, whose use for the production of scaffolds intended for deep wounds treatment is limited, due to its low mechanical and thermal properties. For this reason, until now, it has been used in low amounts and/or in combination with other biopolymers. The aim of the study was to produce thermoplastic filaments (TPS) with high starch content, useful for scaffolds production by Fusion Deposition Modelling 3D printing technique. TPS was obtained by hot melt extrusion from a mixture of starch (70 % w/w) and glycerol (30 % w/w) combined to cationic clay montmorillonite, citric acid and magnesium stearate to improve strength and processability. The prepared scaffold was characterized and compared to other two scaffolds, where the effect of the addition of polycaprolactone (PCL) or methylsulphonylmethane (MSM) (as thermostable model drug) to the blend was evaluated. The mechanical properties were investigated by Brillouin Light Scattering. In vitro studies highlighted that the scaffolds are: i) able to absorb simulated exudates (reaching a hydration of 35 % in 7 days); ii) safe on keratinocytes (viability &gt; 70 %) stimulating their growth; iii) able to inhibit <em>S. pyogenes</em> growth.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114698"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silica-based EGFR-degrading nano-PROTACs for efficient therapy of non-small cell lung cancer","authors":"Lei Fang ,&nbsp;Ruixue Zhu ,&nbsp;Meijing Li ,&nbsp;Junhui Ma ,&nbsp;Sijun Fan ,&nbsp;Xuelian He ,&nbsp;Zhongrui Yang ,&nbsp;Yakai Yan ,&nbsp;Xiang Ma ,&nbsp;Guangya Xiang","doi":"10.1016/j.ejpb.2025.114699","DOIUrl":"10.1016/j.ejpb.2025.114699","url":null,"abstract":"<div><div>Proteolysis targeting chimeras (PROTACs) technology is a promising strategy for degrading proteins of interest. Traditional PROTACs, however, often face challenges such as poor solubility, low stability, and off-target toxicity. To address these challenges, we integrated nanotechnology to enhance the delivery of target-protein degraders to the tumor sites, thereby improving their properties. Here, we report silica-based nano-PROTACs (SiPROTACs) that feature multiple ligands on the surface to target and degrade the transmembrane protein epidermal growth factor receptor (EGFR). SiPROTACs, with a diameter of approximately 50 nm, can efficiently bind to EGFR, recruit cereblon (CRBN) to induce EGFR ubiquitination, and facilitate their degradation by proteasomes. In HCC-827 and PC-9 cell lines, SiPROTACs initiated EGFR degradation at a notably low concentration of 50 nM, demonstrating greater efficiency compared to traditional PROTACs. In HCC-827 xenograft tumor-bearing mice, SiPROTACs accumulated at tumor site for at least 48 h and exhibited significant anti-tumor effects in vivo without causing noticeable side effects. These findings suggest a novel approach for the application of PROTACs highlighting their therapeutic potential for the treatment of non-small cell lung cancer (NSCLC).</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114699"},"PeriodicalIF":4.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}