Journal of Liposome Research最新文献

{"title":"Influence of polyglycerol versus polyethylene glycol coatings on the physicochemical properties and biological performance of liposomes.","authors":"Lin Wu, Xinbi Li, You Huang, Hongjing Chen, Huali Chen, Qianyu Zhang","doi":"10.1080/08982104.2026.2723985","DOIUrl":"https://doi.org/10.1080/08982104.2026.2723985","url":null,"abstract":"<p><p>In recent years, polyglycerol (PG) has received much attention as an alternative to polyethylene glycol (PEG) with adequate biocompatibility and multifunctionality. However, systematic studies comparing the effects of PG- and PEG- coatings on liposomal properties are still lacking, which might provide more insights into their capacity for drug delivery. In this study, polyglycerol (10) stearate (PG-10-MS) was compared with polyethylene glycol (20) stearate (PEG-20-MS) in terms of how these two types of polymeric modifications influenced the physicochemical properties and biological functions of liposomes, with identical hydrophobic anchoring groups and comparable molecular weights for the polymeric moieties. The results demonstrated that both PEGylated and PGylated liposomes possessed excellent physical stability, reduced macrophage uptake <i>in vitro</i>, and prolonged circulation half-life <i>in vivo</i>. Although both polymers conferred hydrophilicity to the liposome surface, they exerted opposing effects on lipid membrane fluidity. On the other hand, PGylated liposomes exhibited superior erythrocyte compatibility, and cytotoxicity was relatively low. Following drug loading, both liposomal formulations showed comparable antitumor efficacy <i>in vitro</i> and <i>in vivo</i>. Collectively, these findings indicated that PGylation showed even superior blood compatibility and comparable drug delivery efficacy to PEGylation, underscoring the potential of PG-based polymers as viable alternatives to PEG.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-16"},"PeriodicalIF":4.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating breast cancer with a transdermal formulation of letrozole-loaded transbilosomes: <i>in vitro</i> and <i>in vivo</i> studies.","authors":"Naifa Alenazi, Zenat Khired, Hussam M Shubaily, Yehia Hazzazi, Mohammed Somailie, Abdullah Ali Alamri, Amani Alhejely, Hassien M Alnashiri, Mari Sumayli, Salama A Salama","doi":"10.1080/08982104.2026.2714171","DOIUrl":"https://doi.org/10.1080/08982104.2026.2714171","url":null,"abstract":"<p><p>Letrozole (LTZ), an aromatase inhibitor, is commonly prescribed to patients with breast cancer (BC). LTZ can induce apoptosis and inhibit tumor angiogenesis. Despite its high efficacy, LTZ is hindered by significant side effects, low bioavailability, and poor solubility, all of which limit its overall effectiveness. The aim of this study was to develop a transdermal formulation of LTZ-loaded transbilosomes (LLT) for treatment of BC. This new formulation can lessen LTZ's toxicity while increasing its solubility, targeting, and efficacy. Multiple LLT formulations were created and tested using Design Expert software to select the optimal one. A DMBA rat model was used to evaluate the efficacy, targeting, and safety of the optimal LLT formulation. The optimal LLT formulation decreased drug release by 69.25%, compared to free LTZ. Compared to the disease group, the tumor volume in the transdermal LLT group decreased by 97.65%. The transdermal LLT formulation increased LTZ accumulation in the tumor by 4.7-fold. Histopathological and toxicity studies confirm the antiproliferative effects and safety of the transdermal LLT formulation. These findings support the potential of transdermal LLT formulation to be an effective and safe treatment for BC.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-13"},"PeriodicalIF":4.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation delivery systems for coenzyme Q10: trends in nanovesicles, penetration enhancers, and bioactivity optimization.","authors":"Ahmed M Saleh, Eman S Shalaby, Heba M Hamama, Soha A Abdel Gawad","doi":"10.1080/08982104.2026.2717256","DOIUrl":"https://doi.org/10.1080/08982104.2026.2717256","url":null,"abstract":"<p><p>Coenzyme Q10 (CoQ10), a lipophilic benzoquinone essential for mitochondrial energy metabolism and intrinsic antioxidant defense, exhibits substantial therapeutic potential in cardiovascular, neurological, dermatological, and metabolic disorders. However, its pronounced hydrophobicity, high molecular weight (863.34 g/mol), thermolability, and extremely poor aqueous solubility significantly limit its oral and topical bioavailability, rendering conventional formulations insufficient for optimal therapeutic outcomes. This review provides a contemporary overview of advanced delivery strategies designed to overcome these limitations, with a primary focus on nano-vesicular drug delivery systems and bioavailability enhancement approaches. The physicochemical and biological characteristics of CoQ10 are discussed to clarify the major barriers restricting its effective administration. Particular emphasis is placed on nano-vesicular platforms, including niosomes, transfersomes, ethosomes, transethosomes, phytosomes, and cubosomes, highlighting their structural attributes, encapsulation efficiency, permeability enhancement, and reported preclinical and clinical outcomes. Additionally, complementary penetration-enhancing approaches, such as chemical permeation enhancers, microneedles, iontophoresis, and biomimetic or hybrid systems, are examined for their role in improving CoQ10 delivery. The relationship between formulation design and biological performance is critically evaluated to provide mechanistic insight into therapeutic enhancement. Available clinical evidence suggests improved systemic absorption and therapeutic efficacy of CoQ10 through lipid-based and nano-vesicular systems, particularly liposomal and phytosomal formulations. Finally, key translational challenges, including formulation stability, biological barriers, manufacturing scalability, and regulatory considerations, are discussed alongside emerging trends such as stimuli-responsive nanocarriers, mitochondria-targeted systems, and computationally guided formulation development. Collectively, these advances highlight the potential of nano-enabled delivery systems to overcome CoQ10 pharmacokinetic limitations and facilitate future clinical translation.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-26"},"PeriodicalIF":4.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of nephrotoxicity and antibacterial activity of free and liposomal gentamicin in rats: Biochemical, molecular and histopathological analysis.","authors":"Murat Celebi, Hasan Susar, Cagla Celebi, Ozhan Karatas, Orkun Babacan, Izzet Karahan","doi":"10.1080/08982104.2026.2715627","DOIUrl":"https://doi.org/10.1080/08982104.2026.2715627","url":null,"abstract":"<p><p>Gentamicin is a widely used aminoglycoside antibiotic; however, its clinical use is limited by dose-dependent nephrotoxicity. Liposomal drug delivery systems may reduce toxicity while preserving antibacterial efficacy. This study aimed to comparatively evaluate the nephrotoxic and antimicrobial effects of free and liposomal gentamicin in a rat model. Rats were divided into control, free gentamicin (FGT; 100 mg/kg), and liposomal gentamicin (LipGT; 100 mg/kg) groups administered for 7 days. Renal function parameters, oxidative stress biomarkers, pro-inflammatory cytokines, renal injury markers, and gene expression levels were analyzed. Free gentamicin significantly increased serum BUN and creatinine levels, oxidative stress, inflammatory cytokines, and renal injury biomarkers. Liposomal gentamicin attenuated these alterations, demonstrating a protective effect. Creatinine levels showed partial normalization, whereas BUN exhibited a distinct response. Liposomal treatment partially restored SIRT3 expression but did not normalize PAX2. Histopathological findings supported these results. Antimicrobial analysis revealed preserved activity against Escherichia coli but reduced efficacy against Staphylococcus aureus. Liposomal encapsulation mitigates gentamicin-induced nephrotoxicity while partially maintaining antibacterial activity, suggesting a promising strategy to improve drug safety.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-12"},"PeriodicalIF":4.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposed Axitinib delivered via lipid-extruded PEGylated liposomes: 2D/3D breast cancer cell evaluation and in-vivo pharmacokinetics.","authors":"Avinash Pawar, Ekta Pardhi, Sumedh Bahadure, Rati Yadav, Santanu Basak, Essha Chatterjee, Santosh Kumar Guru, Neelesh Kumar Mehra","doi":"10.1080/08982104.2026.2712485","DOIUrl":"https://doi.org/10.1080/08982104.2026.2712485","url":null,"abstract":"<p><p>PEGylated liposomal nanocarriers have emerged as a promising drug delivery platform for improving the pharmacokinetic performance and systemic circulation of poorly water-soluble anticancer drugs. In this study, Axitinib-loaded PEGylated liposomes (F11-PEGliposome) were prepared and evaluated for the potential treatment of breast cancer. Liposomes were prepared by optimization with a Box-Behnken design and subsequently extruded using lipid extrusion to obtain a vesicle size of 158.6 ± 2.4 nm, PDI of 0.12 ± 0.01, zeta potential of -1.2 ± 0.5, and entrapment efficiency of 79.9 ± 1.8%. In 2D cell culture studies, F11-PEGliposome showed enhanced anticancer activity with IC₅₀ values of 1.7- and 2.13-fold lower than free Axitinib. Cellular uptake, ROS generation, JC-1 mitochondrial membrane potential, and AO/EB staining assays exhibited enhanced internalization and apoptosis induction. In 3D spheroid models, F11-PEGliposome exhibited deep penetration in the tumor, significant growth inhibition, increased ROS production, and pronounced apoptotic cell death. <i>In-vivo</i> pharmacokinetic and biodistribution studies showed extended circulation, enhanced bioavailability, and prolonged half-life. Reduced hepatic and renal toxicity was evident as shown by histopathological evaluation and decreased serum AST, ALT, creatinine, and BUN levels. Western blot analysis revealed dose-dependent increases of cleaved caspase-3 and cleaved PARP1, supporting the conclusion of apoptosis.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-26"},"PeriodicalIF":4.7,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CS-PEG-modified long-circulating tanshinone I liposomes for enhanced lipid-lowering synergy with atorvastatin and reduced adverse effects.","authors":"Li Zhang, Yize Lv, Xuedi Weng, Yan Gao, Jie Gao, Xia Cao, Michael Adu-Frimpong, Qilong Wang","doi":"10.1080/08982104.2026.2711141","DOIUrl":"https://doi.org/10.1080/08982104.2026.2711141","url":null,"abstract":"<p><p>Chitosan-polyethylene glycol (CS-PEG)-modified long-circulating liposomes were developed and loaded with tanshinone I (TaI@CS-PEG-L) to overcome its poor solubility and low bioavailability, as well as enhance the lipid-lowering efficacy of atorvastatin (At) and mitigate its tissues toxicity. After synthesis of CS-PEG copolymer, it was characterized with infrared and proton nuclear magnetic resonance. Thin-film hydration was used to prepare TaI@CS-PEG-L before optimization was performed using Box-Behnken design. Optimal liposomal formulation was obtained when mass ratio of lecithin:cholesterol:TaI mass ratio was 12:1:1 along with 0.2% CS-PEG, which displayed appropriate particle size (117.41 nm), polydispersity index (0.182), zeta potential (+17.31 mV), encapsulation efficiency (93.15%), and drug loading (5.19%). Besides, the liposomal preparation exhibited good long-term storage stability (over 30 days at 4 °C and 25 °C) and satisfactory gastrointestinal stability in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids for 4 h. TaI@CS-PEG-L displayed increased cellular uptake and in vitro release compared with free TaI and unmodified liposomes. Regarding pharmacokinetic studies, TaI@CS-PEG-L increased AUC_0-ₜ, t₁/₂, and C_max in rats by 7.26-fold, 2.43-fold, and 3.12-fold, respectively, which indicates significantly enhanced oral bioavailability. TaI@CS-PEG-L monotherapy markedly lowered serum lipid levels in hyperlipidemic mice, thereby improving liver function indices, and alleviating pathological liver injury. TaI@CS-PEG-L demonstrated synergistic lipid-lowering effects and efficiently reversed At-induced hepatic and pancreatic injuries after combination with At, thus outperforming free TaI and TaI@L. Therefore, CS-PEG-modified long-circulating liposomes could efficiently address delivery challenges of TaI, thereby yielding a formulation that could potently lower serum lipid levels and protect liver against injury. The findings of this study offer a promising 'efficacy-enhancing and toxicity-reducing' strategy for potential treatment of hyperlipidemia in the clinics.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-19"},"PeriodicalIF":4.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A quality-by-design engineering strategy for hybrid lipid-random copolymer nanoparticles optimization: methotrexate loading and effectiveness studies.","authors":"Efstathia Triantafyllopoulou, Ilias Papantzimas, Anastasia Balafouti, Paraskevi Papakyriakopoulou, Lefkothea Antonara, Maria Gazouli, Dimitrios M Rekkas, Georgia Valsami, Stergios Pispas, Natassa Pippa","doi":"10.1080/08982104.2026.2701968","DOIUrl":"https://doi.org/10.1080/08982104.2026.2701968","url":null,"abstract":"<p><p>The quality by design approach supports the rational development of pharmaceutical formulations. This strategy is particularly valuable in the case of hybrid nanoparticles, where complex molecular interactions pose challenges to predictability, control, and therapeutic performance. In this study, based on preliminary findings, hybrid nanoparticles were developed and optimized using 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine and a statistical (random) copolymer, composed of oligo (ethylene glycol) methyl ether methacrylate and lauryl methacrylate incorporating a hydrophobic model drug-methotrexate. The effects of random copolymer concentration and drug content were investigated as critical formulation variables influencing key quality attributes. Additionally, nanoparticles stability under storage and biorelevant conditions was assessed. The most promising formulations were further evaluated for their <i>in vitro</i> anticancer efficacy using glioblastoma primary cells demonstrating encouraging results. It is anticipated that this research will shed light on the rational design of hybrid drug delivery systems combining well-established phospholipids and innovative random copolymers.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-11"},"PeriodicalIF":4.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel quantification method for unencapsulated doxorubicin in tissues: unlocking PK/PD and TK/TD insights for pegylated liposomal doxorubicin.","authors":"Koki Narimatsu, Masahiro Yahata, Mei S Yamaguchi, Takao Watanabe, Izuru Miyawaki","doi":"10.1080/08982104.2026.2700508","DOIUrl":"https://doi.org/10.1080/08982104.2026.2700508","url":null,"abstract":"<p><p>Pegylated liposomal doxorubicin (PLD) is the first FDA-approved liposomal product in the oncology field and has been extensively investigated over the years. Although PLD has been extensively studied, measurement of unencapsulated doxorubicin in tissues remains technically challenging, limiting detailed interpretation of tissue pharmacokinetics/pharmacodynamics (PK/PD) and toxicokinetics/toxicodynamics (TK/TD) relationships. Here, we present a novel approach to quantify unencapsulated doxorubicin in tumors and other tissues. Our method employs the gentleMACS Dissociator for tissue homogenization to prevent liposome disruption. While homogenization with conventional zirconia beads increased the unencapsulated doxorubicin fraction by 4.2- to 13.3-fold, homogenization with the gentleMACS Dissociator resulted in no increase in unencapsulated doxorubicin, demonstrating superior preservation of PLD integrity compared with conventional techniques. Moreover, homogenization of freeze-thawed tissue samples did not induce doxorubicin release, enabling sample cryopreservation prior to analysis. Using this approach, we observed a 3.7-fold higher fraction of unencapsulated doxorubicin relative to total (encapsulated + unencapsulated) concentration in tumors than in liver. This difference may reflect enhanced release and/or prolonged retention of released doxorubicin in tumors, as well as more rapid elimination of released doxorubicin in the liver. Our method is expected to provide critical insights into doxorubicin release from liposomes and the retention of released doxorubicin thereby facilitating the PK/PD and TK/TD analysis of liposomal products. By addressing a fundamental need in liposomal analysis, our method holds significant promise for accelerating drug development and improving cancer therapy outcomes.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-9"},"PeriodicalIF":4.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon monoxide-releasing vesicles provide rapid and sustained inhibition of inflammatory pain in mice.","authors":"Alejandra Bárcena-Esplá, Mario López-Martín, Sylmara Esther Negrini-Ferrari, Ignacio Martínez-Martel, Maribel Marín-García, Ramon Barnadas-Rodríguez, Olga Pol","doi":"10.1080/08982104.2026.2691577","DOIUrl":"https://doi.org/10.1080/08982104.2026.2691577","url":null,"abstract":"<p><p>Carbon monoxide (CO) is an important modulator of chronic pain, but its clinical use remains limited. To enhance its therapeutic potential, we developed a vesicular CO-releasing system based on a carbonyl metallosurfactant (PCOL6) and soy phosphatidylcholine (SPC) and evaluated its physicochemical properties, as well as its <i>in silico</i> and <i>in vivo</i> effects on inflammation-induced nociception and muscle impairment in male C57BL/6 mice. The metallosomes exhibited a uniform size distribution, stability upon dilution, and a predominantly single membrane, indicating their suitability for therapeutic applications. Computational simulations revealed that PCOL6 can mix with phospholipids to form stable lamellar structures with thinner and more disordered bilayers than those of pure phospholipid membranes. <i>In vivo</i> experiments showed that acute administration of PCOL6/SPC vesicles inhibited complete Freund's adjuvant (CFA)-induced allodynia faster and longer than tricarbonyldichlororuthenium (II) dimer, Ru₂Cl₄(CO)₆ (CORM-2). Repeated metallosome treatment was also more effective than CORM-2 at reducing allodynia, hyperalgesia, and inflammation-related muscle deficits. Both CO releasers normalized CFA-induced NOD-like receptor protein 3 inflammasome overexpression, increased heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 expression, and maintained elevated superoxide dismutase 1 levels in paw tissues; notably, HO-1 induction was greater in PCOL6/SPC-treated mice. These findings suggest that PCOL6/SPC metallosomes represent a promising therapeutic strategy for chronic inflammatory pain.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-13"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Box-Behnken design to optimize erlotinib-niclosamide co-loaded liposomes, overcoming EGFR-mutated lung cancer resistance, and improving sensitivity <i>via</i> EGFR/STAT3 signaling pathway.","authors":"Amruta Prabhakar Padakanti, Mythri Chandrasekaran, Suchita Shalini, Sudhagar Selvaraju, Naveen Chella","doi":"10.1080/08982104.2026.2687649","DOIUrl":"https://doi.org/10.1080/08982104.2026.2687649","url":null,"abstract":"<p><p>The co-administration of niclosamide (NCM) with erlotinib hydrochloride (ERL) has been shown to restore ERL sensitivity in resistant non-small cell lung cancer. However, the poor physicochemical properties of both molecules necessitate a specialized delivery system for improved delivery and efficacy. Box-Behnken design was used to evaluate the key variables affecting NCM-ERL-Liposome characteristics. The design yielded a broader design space for the selected factors that can achieve superior attributes, including particle size of 93.42 ± 2.41 nm, polydispersity index of 0.356 ± 0.01, zeta potential of -9.40 ± 0.59 mV, and maximal entrapment efficiencies (NCM: 77.97 ± 2.25%; ERL: 72.75 ± 1.49%). Trehalose showed better redispersion and good physical stability, as confirmed from ATR-IR/PXRD/DSC. The formulation demonstrated sustained dual-drug release, stability for three months at 4 ± 2 °C, and hemocompatibility with minimal hemolysis. In-vitro studies showed that NCM restored ERL sensitivity, with lower IC₅₀ values (HCC827-P: 11.27 ± 4.04 µg/mL; HCC827-ER: 7.59 ± 0.62 µg/mL) than those of pure drugs or the physical mixture. The prepared NCM-ERL-Liposomes showed enhanced internalization, triggered caspase-3/7-mediated apoptosis (1.42-fold increase), and suppressed p-EGFR/p-STAT3, indicating adequate payload protection and targeted intracellular release. These results establish a translational platform that requires PK/PD studies in resistant NSCLC models to support precision oncology therapeutics.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"1-16"},"PeriodicalIF":4.7,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}