Hannan Sadiq , Muneeb Ur Rahman , Habiba Akram , Ihtesham Ur Rehman , Rehan Ali , Rehan Khan
{"title":"Organelle-targeted nanostructured lipid carriers: Strategic design, analytical validation, and translational insights for precision intracellular drug delivery","authors":"Hannan Sadiq , Muneeb Ur Rahman , Habiba Akram , Ihtesham Ur Rehman , Rehan Ali , Rehan Khan","doi":"10.1016/j.jddst.2025.107590","DOIUrl":"10.1016/j.jddst.2025.107590","url":null,"abstract":"<div><div>Precision intracellular drug delivery, enhanced payload capacity, physicochemical stability, and tunable release kinetics are the features offered by nanostructured lipid carriers (NLCs) as a next-generation drug delivery platform. Organelle-specific engineering and rational design of NLCs for targeted delivery to subcellular compartments, including the mitochondria, lysosomes, nucleus, endoplasmic reticulum (ER), and Golgi apparatus, are comprehensively discussed in this review. Strategic physicochemical modifications, such as particle size optimisation, surface functionalization with targeting ligands (e.g., TPP, TAT, NLS, KDEL), ceramide-mimetic components, and incorporation of pH or redox-responsive lipids, achieve organelle-specific localization, enabled by coupling chemistries like bio-orthogonal click reactions and EDC/NHS activation. High-resolution imaging modalities (CLSM, TEM, cryo-EM), co-localization quantification (Pearson's and Mander's coefficients), LC-MS/MS, FERT, FRAP, imaging flow cytometry, and differential scanning calorimetry (DSC) are used to validate targeting efficiency and formulation integrity analytically. Particle size, zeta potential, encapsulation efficiency, crystallinity, and release behavior are included in critical quality attributes (CQAs) that are optimised systematically using Design of Experiment (DoE) within a quality-by-design (QbD) framework. Physiologically based pharmacokinetics (PBPK) modelling and spatial lipidomics for assessing biodistribution and pharmacodynamic impact are used as preclinical translation, incorporating bioanalytical method validation. Endosomal entrapment, interspecies variability, and GMP-compliant challenges are the key translational and regulatory bottlenecks addressed in this review. Transformative potential for NLC-based precision medicine includes converging dual-organelle targeting, multi-stimuli responsiveness, emerging AI-guided design tools, and continuous manufacturing platforms. Redefining the landscape of intracellular therapeutics towards clinically viable organelle-targeted formulations through cutting-edge innovations is consolidated in this review.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107590"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryam Sharifiaghdam , XuXin Sun , Ada W.Y. Leung , Nancy Dos Santos , Nicole Wretham , Zeynab Nosrati , Marcel B. Bally
{"title":"Liposomal Formulations of Metal-CX5461 complexes: Copper-CX5461 complexation mediates CX5461 degradation while Zinc-CX5461 formulations are suitable for development","authors":"Maryam Sharifiaghdam , XuXin Sun , Ada W.Y. Leung , Nancy Dos Santos , Nicole Wretham , Zeynab Nosrati , Marcel B. Bally","doi":"10.1016/j.jddst.2025.107586","DOIUrl":"10.1016/j.jddst.2025.107586","url":null,"abstract":"<div><div>Copper (Cu<sup>2+</sup>) ions have facilitated the encapsulation of CX5461 within liposomes and the formulations showed promising anticancer potential as judged by <em>in-vivo</em> studies. In our attempt to translate this formulation into a product suitable for use in formal pre-clinical safety pharmacology studies, we uncovered a problem. In this report, studies have demonstrated that Cu mediated CX5461 encapsulation within DSPC/Chol (55:45 mol%) and DMPC/Chol (55:45 mol%) liposomes can lead to instability of CX5461. Chromatographic analysis revealed that CX5461 degradation increases as the incubation temperature increased from 40 °C to 60 °C. The change in CX5461 structure results in the emergence of new peaks detected by HPLC and this is associated with a reduction in the parent drug. The rate of CX5461 degradation was influenced by incubation time and liposome lipid composition. When encapsulated in the DSPC/Chol:Cu(CX5461) liposome formulation, just 1 h of incubation at 40 °C or 60 °C resulted in greater than 50 % CX5461 degradation. This degradation was associated with a 1.7-fold and a 3.8-fold decrease in the CX5461 to liposomal lipid ratio within 1 h at 40 °C and 60 °C, respectively. When the CX5461 formulation was prepared using DMPC/Chol liposomes, CX5461 was less prone to degradation. Significant decrease in the CX5461 to liposomal lipid ratio for this formulation required 6 h of incubation at 40 °C or 60 °C. Surprisingly, even after complete degradation of CX5461, the degraded compounds were therapeutically as active as parent CX5461 based on <em>in-vitro</em> cytotoxicity studies. This suggested that the biologically active portion of CX5461 was maintained even after Cu-mediated degradation. Regardless, the extent and rate of degradation preclude the pharmaceutical development of the copper formulation as the active ingredient instability poses significant (perhaps insurmountable) challenges for chemistry, manufacturing, and control documentation. To overcome this limitation, we shifted to zinc as an alternative metal to complex CX-5461. Preliminary data demonstrate that Zn(CX5461) enables efficient liposomal encapsulation while preserving chemical stability.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107586"},"PeriodicalIF":4.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sukaina Nimrawi , Nusaiba K. Al-nemrawi , Young M. Kwon
{"title":"Advancements in delivering RNA therapies using physical transdermal drug delivery methods","authors":"Sukaina Nimrawi , Nusaiba K. Al-nemrawi , Young M. Kwon","doi":"10.1016/j.jddst.2025.107587","DOIUrl":"10.1016/j.jddst.2025.107587","url":null,"abstract":"<div><div>RNA therapies, including mRNA, siRNA, and miRNA, hold tremendous potential for treating various pathological conditions, ranging from cancer to genetic disorders. However, their successful clinical application depends on the development of efficient and patient-friendly delivery systems. This review explores advancements in physical transdermal drug delivery (TDD) methods as innovative platforms for delivering RNA therapeutics. Techniques such as microneedles, iontophoresis, electroporation<strong>,</strong> sonophoresis, jet injections, and laser radiation are highlighted for their ability to overcome traditional delivery challenges, enabling localized and systemic RNA delivery through the skin with enhanced stability, efficacy, controlled release, and reduced patient discomfort. The review provides a comprehensive overview of the principles, mechanisms, and advantages of these methods, along with a detailed summary of recent studies in the literature, highlighting future research and clinical application opportunities.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107587"},"PeriodicalIF":4.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Puja Kumari, Srijita Sen, Atul Pandurang Kumbhar, Bishwarupa Darshan Dash, Hemant Kushwah, Abhishek Dhabe, Ankit Kumar Singh, Om Prakash Ranjan
{"title":"PVA/pectin based electrospun nanofibers loaded with tranexamic acid for hemostasis: Preparation, in-vitro characterization, and in-vivo evaluation","authors":"Puja Kumari, Srijita Sen, Atul Pandurang Kumbhar, Bishwarupa Darshan Dash, Hemant Kushwah, Abhishek Dhabe, Ankit Kumar Singh, Om Prakash Ranjan","doi":"10.1016/j.jddst.2025.107593","DOIUrl":"10.1016/j.jddst.2025.107593","url":null,"abstract":"<div><div>Nanofibers can be used to mitigate issues that are present with the current treatment for hemorrhage. A hemostatic agent should control the bleeding quickly and prevent the solubilization of the formed clot in a biocompatible way. A nanofiber mat of PVA-Pectin loaded with tranexamic acid (TXA) has been prepared to control hemorrhage. A series of characterizations, like SEM, XRD, ATR-IR, DSC, and tensile strength, were determined. HPLC studies have been done to check the encapsulation and <em>in vitro</em> release of the drug in the nanofiber mat. Different important attributes for hemostasis have been measured <em>in vitro</em> in blood-clotting and plasma recalcification time studies. Hemostasis performance has been verified in terms of bleeding time and blood loss in the tail amputation model. It has been found that the polymers selected for the nanofabrication have significant hemostatic properties, which enhance the effect of tranexamic acid (TXA). The application of TXA-nanofiber has been shown to control the release of TXA at the injury site and prevent multiple rebleeding. The developed nanofiber mat loaded with tranexamic acid demonstrates a great approach to induce rapid hemostasis without secondary bleeding in prehospital settings.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107593"},"PeriodicalIF":4.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aimon Qureshi , Hafiz Shoaib Sarwar , Muhammad Sarfraz , Huma Hameed , Mahjabeen Akbar , Mahtab Ahmad Khan , Fareeha Anwar , Malik Ihsanullah Khan , Omer Salman Qureshi , Muhammad Farhan Sohail
{"title":"Thiomer-coated solid lipid nanoparticles for the glutathione and temperature-responsive drug delivery against breast cancer","authors":"Aimon Qureshi , Hafiz Shoaib Sarwar , Muhammad Sarfraz , Huma Hameed , Mahjabeen Akbar , Mahtab Ahmad Khan , Fareeha Anwar , Malik Ihsanullah Khan , Omer Salman Qureshi , Muhammad Farhan Sohail","doi":"10.1016/j.jddst.2025.107579","DOIUrl":"10.1016/j.jddst.2025.107579","url":null,"abstract":"<div><div>Breast cancer is the most prevalent type of cancer among women. Despite extensive efforts, existing cancer therapies often yield suboptimal outcomes due to their inherent off-target toxicity and the emergence of multidrug resistance in tumor cells. Thus, there exists a pressing need to explore innovative nanotechnology-based drug delivery systems to address these challenges. The present study aimed to develop temperature and glutathione (GSH)-responsive nanocarriers to selectively deliver 5-Fluorouracil (5-FU) to the breast cancer tumor. For this purpose, 5-FU loaded temperature-sensitive solid lipid nanoparticles (SLNs) were formulated using Lauric Acid and Oleic acid-based binary mixture with a melting range of 39–42 °C. A glutathione-responsive polymeric coating of folate grafted thiolated chitosan (FTCS) was coated onto developed lipid cores and evaluated in terms of physicochemical characterization, <em>in-vitro</em> drug release in normal physiological conditions as well as in the presence of glutathione and at a temperature of 39 °C. Evaluation of anticancer activities was carried out in vitro using MDA-MB-123 cancer cell lines and <em>in-vivo</em> in a chemical-induced breast cancer rat model. FTCS-SLN-5-FU exhibited an average size of 274.6 ± 2.62 nm and zeta potential of +18.74 ± 0.22 mV as compared to non-coated 5-FU loaded nanoformulation (SLN-5-FU) with average particle size of 184 ± 20.51 nm and zeta potential of 19 ± 0.27 mV, thus confirming the successful coating of the cationic FTCS. The SEM images of formulations showed well-defined nano-sized particles. <em>In-vitro</em> drug release studies have confirmed the glutathione and temperature-sensitive behavior of FTCS-SLN-5-FU, indicating 80.32 ± 8.5 % of 5-FU release at pH 5.8, 39 °C temperature in the presence of 20 mM glutathione compared to 10.21 % ± 1.89 % of drug release at pH 7.4 during the first 24 h. Invitro anticancer activity revealed a significantly reduced viability in the case of FTCS-SLN-5-FU compared to SLN-5-FU. Similarly, <em>In-vivo</em> anticancer activity in breast cancer-induced rat models indicated significantly reduced tumor weight compared to SLN-5-FU and 5-FU. The results provided proof of the concept that utilizing temperature and GSH-sensitive nanocarriers can be a suitable strategy to enhance the intratumoral delivery and thus anticancer activity of the drugs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107579"},"PeriodicalIF":4.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barbara Bigi , Francesca Bertini , Claudia Mari , Laura Di Muzio , Stefania Cesa , Letizia Angiolella , Andrea Giammarino , Gustavo Giusiano , Stefania Garzoli , Maria Antonietta Casadei , Patrizia Paolicelli , Stefania Petralito
{"title":"Improved antifungal activity of Origanum vulgare L. essential oil in phospholipid-based nanoemulsions: Role of co-surfactants and surface charge","authors":"Barbara Bigi , Francesca Bertini , Claudia Mari , Laura Di Muzio , Stefania Cesa , Letizia Angiolella , Andrea Giammarino , Gustavo Giusiano , Stefania Garzoli , Maria Antonietta Casadei , Patrizia Paolicelli , Stefania Petralito","doi":"10.1016/j.jddst.2025.107582","DOIUrl":"10.1016/j.jddst.2025.107582","url":null,"abstract":"<div><div>This study investigates the antifungal efficacy of <em>Origanum vulgare</em> L. essential oil (OEO) encapsulated in phospholipid-based nanoemulsions (NEs) against <em>Candida albicans</em>. The formulations were developed using different amounts of soy phosphatidylcholine (SoyPC) and co-surfactants and/or charge-inducing agents, with the aim of enhancing the stability and bioactivity of OEO. Our results demonstrate that all nanoemulsion formulations significantly outperformed non-formulated OEO in terms of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), regardless of surface charge. The inclusion of co-surfactants and/or charge-inducing agents was critical in maintaining the biological efficacy of the NEs over time, primarily by improving colloidal stability and enabling sustained release of the encapsulated active compounds. While cationic surfactants are typically associated with enhanced bioactivity, our findings suggest that stable, negatively charged formulations can achieve comparable antifungal activity without the potential toxicity of cationic agents. Replacing OEO with pure carvacrol allowed for a more accurate evaluation of formulation performance, highlighting the importance of release kinetics and structural integrity, rather than over surface charge, in determining antifungal efficacy. In addition, the study emphasizes the need for careful characterization of essential oil composition post-formulation and calls for further analytical investigation into the behavior of volatile components during emulsification. These insights are pivotal for the rational design and optimization of nanoemulsion-based antimicrobial systems incorporating essential oils.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107582"},"PeriodicalIF":4.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrícia C. Pires , Mariana Magalhães , Célia Cabral , Francisco Veiga , Priscila Gava Mazzola , Ana Cláudia Paiva-Santos
{"title":"Development and characterization of novel intranasal in situ thermoreversible ketoprofen-loaded nanoemulgels for the treatment of glioblastoma","authors":"Patrícia C. Pires , Mariana Magalhães , Célia Cabral , Francisco Veiga , Priscila Gava Mazzola , Ana Cláudia Paiva-Santos","doi":"10.1016/j.jddst.2025.107580","DOIUrl":"10.1016/j.jddst.2025.107580","url":null,"abstract":"<div><div>Ketoprofen (KET) has been proven effective against glioblastoma. Nevertheless, its hydrophobic nature and susceptibility to degradation upon administration, added to the blood-brain barrier's low permeability, make its repurposing for brain cancer treatment challenging. Having this in mind, the purpose of this work was to develop KET-loaded <em>in situ</em> thermoreversible nanoemulgels for intranasal nose-to-brain delivery, aiming at increased drug strength and protection, controlled drug release, and improved bioavailability. Formulations containing Capryol® 90, Tween® 80, Transcutol® HP, poloxamer 407, and water were produced through spontaneous emulsification. Formulations' droplet size, polydispersity index (PDI), zeta potential, pH, rheology, stability, <em>in vitro</em> drug release, and <em>in vitro</em> antitumor efficacy and safety were evaluated. A high drug strength (4 mg/mL), and small (20–30 nm) and monodisperse (PDI 0.1–0.2) nanodroplets, with slightly negative to neutral zeta potential (−1.5 to −10 mV), were obtained. The nanoemulgels' also revealed skin adequate pH (≈6), nasal cavity temperature’ sol-gel transitions (32 °C), elevated viscosity (13660–927302 cP), and high cumulative controlled <em>in vitro</em> drug release (≈78–93 %), following Makoid-Banakar and Weibull kinetic models. Optimized nanoemulgels revealed relevant efficacy against human glioblastoma U87 cells. Therefore, intranasal thermoreversible KET-loaded nanoemulgels were successfully developed, of innovative composition, showing promising results for glioblastoma treatment. Given their high scalability potential, the developed nanoplatforms could be promising candidates for translational applications, and future <em>in vivo</em> assays could further confirm their potential, so that they might one day be considered as an adjuvant or primary treatment for glioblastoma.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107580"},"PeriodicalIF":4.9,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iqra Khan , Rabia Arshad , Waqar Aman , Kashif Barkat , Abdul Malik , Tanveer A. Tabish , Nikhat J. Siddiqi
{"title":"Novel mucoadhesive lysine based glycated self-nanoemulsifying drug delivery system for targeted delivery against respiratory infection","authors":"Iqra Khan , Rabia Arshad , Waqar Aman , Kashif Barkat , Abdul Malik , Tanveer A. Tabish , Nikhat J. Siddiqi","doi":"10.1016/j.jddst.2025.107574","DOIUrl":"10.1016/j.jddst.2025.107574","url":null,"abstract":"<div><div>The aim of this study was to improve the therapeutic efficacy, drug delivery and physicochemical features of antimicrobial peptides (AMPs) L-Lysine, for chronic obstructive pulmonary disease (COPD) by developing a glycosylated self-nanoemulsifying drug delivery system (SNEDDS). Roflumilast (Rof) a phosphodiesterase 4 (PDE4) inhibitor, was entrapped within the SNEDDS system (Glucolysinated Rof SNEDDS) for targeted COPD treatment. The Glucolysinated Rof SNEDDS were successfully formulated and characterized in terms of physicochemical properties, in vitro as well as in vivo efficacy. Conjugation chemistry was confirmed using FTIR spectroscopy, mean droplet size of SNEDDS was 222 ± 0.46 nm, with 0.42 ± 0.11 PDI and −24.3 ± 1.20 mV zeta potential. The formulation demonstrated outstanding mucoadhesion capabilities, with a 95 % improvement in drug entrapment efficiency and 80 % sustained drug release over 12 h. Toxicity assessments were conducted by Pharmacokinetics approaches, which confirmed the formulation's safety. Strong antibacterial action was revealed against <em>Pseudomonas aeruginosa</em>, which disrupt bacterial membrane integrity as demonstrated with SEM imaging. PDE4 inhibition was confirmed by strong binding energy in docking analysis. Serum biochemistry analysis remained constant throughout treatment, and histopathological investigations indicated the shielding effect of excipients used. These results presented, highlight the potential of Glucolysinated Rof SNEDDS as a novel and effective drug delivery system for targeted COPD therapy, synergizing therapeutic efficacy with biocompatibility.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107574"},"PeriodicalIF":4.9,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fenofibrate nano-suspension formulation using hot melt emulsion followed by precipitation","authors":"Meketaye Endeshaw , Sameer V. Dalvi , Indumathi Sathisaran , Tadelle Mekonen , Tebelay Andualem","doi":"10.1016/j.jddst.2025.107576","DOIUrl":"10.1016/j.jddst.2025.107576","url":null,"abstract":"<div><div>Fenofibrate is a pharmaceutical drug of the fibrate class, which is used to lower abnormal lipid levels in the blood. However, fenofibrate suffers from poor bioavailability due to its hydrophobic nature and negligible water solubility. The generation of nanosuspension with increased surface area is one of the mechanisms to minimize this challenge. In this work, fenofibrate nanosuspension was formulated to improve the solubility of the drug. A method of hot melt emulsification followed by precipitating the hot melt into a cold aqueous medium was employed to generate the nanosuspension. Ultrasound energy and stabilizers such as Hydroxymethyl cellulose (HPMC), Polyvinyl Pyrrolidone (PVP), and Bovine Serum Albumin (BSA), along with surfactants including Tween 80 (T80) and Sodium Lauryl Sulphate (SLS), were used to control particle growth and improve the stability of the resulting suspension. Sunflower oil was used as a co-additive agent. The effects of surfactants, ultrasound energy and sonication time, drug to surfactant ratio, and sunflower oil on particle size and suspension stability were investigated. The use of ultrasound sonication during both the hot-melt formation step and the precipitation step produced smaller particle sizes. A ground mixture of fenofibrate with BSA and SLS, in the presence of 3 mL sunflower oil, produced a nanosuspension with particle sizes below 100 nm, exhibiting a relatively lower particle growth rate and improved stability. Using a lower molecular weight BSA surfactant and incorporating sunflower oil produced substantial improvement in the particle size reduction and enhancement of the suspension's stability.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107576"},"PeriodicalIF":4.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Camila Marques , Paulo Cardoso da Costa , Hugo Gonçalves , José Catita , Sérgia Velho , Maria Helena Amaral
{"title":"Development, optimization, and characterization of docetaxel-loaded nanostructured lipid carriers for gastric cancer treatment","authors":"Ana Camila Marques , Paulo Cardoso da Costa , Hugo Gonçalves , José Catita , Sérgia Velho , Maria Helena Amaral","doi":"10.1016/j.jddst.2025.107571","DOIUrl":"10.1016/j.jddst.2025.107571","url":null,"abstract":"<div><div>Gastric cancer remains a pressing health issue, with its global incidence projected to increase in the coming decades. Docetaxel, a widely used chemotherapeutic agent, is recommended for gastric cancer treatment, either as monotherapy or in combination with other drugs. However, its clinical performance is compromised by poor physicochemical properties, systemic and dose-limiting toxicities, drug resistance, and hypersensitivity reactions associated with marketed formulations. Integrating nanotechnology into drug delivery systems offers a forward-looking solution to these persistent challenges.</div><div>In this study, a rational design strategy was applied to develop and optimize nanostructured lipid carriers (NLC) for the localized delivery of docetaxel to gastric cancer cells. The resulting NLC dispersions were thoroughly characterized regarding colloidal stability, morphology, drug incorporation, <em>in vitro</em> release, drug-lipid interactions, thermal behavior, crystallinity, and cytotoxicity. Docetaxel-loaded NLC exhibited a uniform particle size (∼161 nm) and a zeta potential more negative than −20 mV, maintaining predefined quality standards over six months of storage at 4 °C and 25 °C. Approximately 98 % of docetaxel was incorporated, likely in an amorphous or molecularly dispersed state, within the semi-crystalline lipid matrix. A slow and sustained release profile was also obtained. Cell viability analysis at 48 h revealed that docetaxel-loaded NLC were more cytotoxic than the free drug at concentrations of 0.005 nM in AGS cells and 1 nM and 10 nM in NCI-N87 cells. The enhanced efficacy was driven by DTX entrapment, with no observed toxicity from the carrier. These findings suggest that the developed NLC could be a promising delivery system for improving docetaxel therapy in gastric cancer.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107571"},"PeriodicalIF":4.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}