Pharmaceutics最新文献

{"title":"Simvastatin-Loaded Chitosan-Functionalized PLGA Nanoparticles: Characterization and Use in Intimal Hyperplasia Therapy.","authors":"Ashley A Peters, Chanpreet Kaur, Maleen Cabe, Kelly A Langert, Kristopher Maier, Vivian Gahtan","doi":"10.3390/pharmaceutics17030391","DOIUrl":"10.3390/pharmaceutics17030391","url":null,"abstract":"<p><p><b>Background</b>: Statins have beneficial pleiotropic effects, including reducing intimal hyperplasia (IH), but off-target effects remain a concern. Here, we tested the hypothesis that chitosan-functionalized polymeric nanoparticles (NPs) loaded with simvastatin (SL-cNPs) would (1) readily associate with endothelial cells (ECs) and vascular smooth muscle cells (VSMCs); (2) affect EC and VSMC function; and (3) reduce IH compared to systemic simvastatin. <b>Methods</b>: Human aortic ECs and VSMCs were cultured with fluorescently labeled SL-cNPs. The association of SL-cNPs was assessed by immunostaining and flow cytometry. The effect of SL-cNPs, empty cNPs (E-cNPs), and free simvastatin on cells was determined using qRT-PCR for RhoA and RhoB. Carotid artery balloon-injured rats were treated intraoperatively with intraluminal saline, E-cNPs, low- or high-dose SL-cNPs, periadventitial high-dose SL-cNPs, or with pre- and post-operative oral simvastatin plus intraoperative intraluminal saline or low-dose SL-cNPs. Rats were euthanized (day 14) and IH was quantified. <b>Results</b>: SL-cNPs readily associated with ECs and VSMCs. Low- and high-dose SL-cNPs induced significant increases in EC and VSMC RhoA gene expression. High-dose SL-cNPs induced a significant increase in EC RhoB expression, while free simvastatin and low- and high-dose SL-cNPs significantly increased RhoB expression in VSMCs. In vivo, oral simvastatin plus intraluminal SL-cNPs significantly reduced IH compared to controls. <b>Conclusions</b>: cNPs can be used as a vehicle to locally deliver statins to vascular cells. However, other NP formulations may be preferential for IH reduction given only the combination of oral simvastatin and SL-cNPs effectively reduced IH.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physicochemical Characterization and Oral Bioavailability of Curcumin-Phospholipid Complex Nanosuspensions Prepared Based on Microfluidic System.","authors":"Bo Zhang, Wenjing Guo, Zhenyu Chen, Yaxin Chen, Ruining Zhang, Minchen Liu, Jian Yang, Jiquan Zhang","doi":"10.3390/pharmaceutics17030395","DOIUrl":"10.3390/pharmaceutics17030395","url":null,"abstract":"<p><p><b>Background</b>: Curcumin has been proved to have promising prospects in the fields of anti-inflammation, antibacterial, anti-oxidation, and neuroprotection. However, its poor water solubility and stability in strong acid, as well as fast metabolism, lead to low bioavailability, making it difficult to develop further. This study aimed to improve the bioavailability of curcumin by using microfluidic preparation technology. <b>Methods</b>: Using a self-built microfluidic system, polyvinylpyrrolidone K30 and sodium dodecyl sulfate were used as stabilizers to further prepare curcumin-phospholipid complex nanoparticles (CPC-NPs) on the basis of curcumin-phospholipid complex (CPC). The CPC-NPs were characterized and evaluated by X-ray powder diffraction (XRD), differential scanning caborimetry (DSC), dynamic light scattering, and transmission electron microscopy (TEM). Blood samples were collected from rats after oral administration of curcumin, CPC, curcumin nanoparticles (CUR-NPs), and CPC-NPs, respectively. The pharmacokinetics were analyzed by enzymatic digestion and HPLC. <b>Results</b>: The optimized CPC-NPs had a particle size of 71.19 ± 1.37 nm, a PDI of 0.226 ± 0.047, and a zeta potential of -38.23 ± 0.89 mV, which showed a spherical structure under TEM and good stability within 5 days at 4 °C and 25 °C. It was successfully characterized by XRD combined with DSC, indicating the integrational state of curcumin-soy lecithin and conversion to an amorphous form. The results of the pharmacokinetic study showed that the C_max of curcumin, CUR-NPs, CPC, and CPC-NPs were 133.60 ± 28.10, 270.23 ± 125.42, 1894.43 ± 672.65, and 2163.87 ± 777.36 ng/mL, respectively; the AUC_0-t of curcumin, CUR-NPs, CPC, and CPC-NPs were 936.99 ± 201.83, 1155.46 ± 340.38, 5888.79 ± 1073.32, and 9494.28 ± 1863.64 ng/mL/h. <b>Conclusions</b>: CPC-NPs prepared by microfluidic technology had more controllable quality than that of traditional preparation and showed superior bioavailability compared with free drug, CPC, and CUR-NPs. Pharmacodynamic evaluation of anti-inflammatory, anti-oxidation, and neuroprotection needs to be confirmed in follow-up studies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ciprofloxacin-Loaded Spray-Dried Lactose Particles: Formulation Optimization and Antibacterial Efficacy.","authors":"Sai Liu, Simon Gaisford, Gareth R Williams","doi":"10.3390/pharmaceutics17030392","DOIUrl":"10.3390/pharmaceutics17030392","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Bacterial infections in the oral cavity and outer ear require effective and targeted drug delivery systems. This study details the production of drug-loaded lactose microparticles, with the aim of creating antibiotic formulations for ultimate use in combatting oral and outer ear bacterial infections. <b>Methods</b>: Lactose particles were prepared via spray drying and optimized with varying ciprofloxacin (cipro) loadings to maximize the drug content. The particles were characterized to evaluate their performance in terms of physicochemical properties, drug-loading efficiency, drug-release kinetics, and antibacterial activity. <b>Results</b>: The resulting particles exhibited spherical morphology, efficient cipro loading (in the range of 1.1-52.9% <i>w</i>/<i>w</i>) and rapid cipro release within 5 h (achieving 70-81% release). In addition, they demonstrated effective concentration-dependent antibacterial activity against gram-positive <i>Staphylococcus aureus</i> and gram-negative <i>Pseudomonas aeruginosa</i>, with bacterial growth effectively inhibited for more than 24 h when particle concentrations reached the minimum inhibitory concentration. <b>Conclusions</b>: These findings highlight the potential of spray-dried cipro loaded lactose particles as an efficient approach for localized antibacterial treatment, offering a promising solution for managing bacterial infections in the oral cavity and outer ear.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 20th Anniversary of Pegaptanib (MacugenTM), the First Approved Aptamer Medicine: History, Recent Advances and Future Prospects of Aptamers in Therapy.","authors":"Miklós Bege, Rasha Ghanem Kattoub, Anikó Borbás","doi":"10.3390/pharmaceutics17030394","DOIUrl":"10.3390/pharmaceutics17030394","url":null,"abstract":"<p><p>In addition to classic small-molecule drugs and modern protein-based biologics, an intriguing class of medicines is the therapeutic oligonucleotides. Most approved drugs in this category are antisense oligomers or those acting via RNA interference, both of which use base hybridization. Aptamers, also known as chemical antibodies form a smaller, yet equally interesting group of oligonucleotides that can recognize a wide range of molecular targets. Despite their high potential, only two aptamers have been approved to date, pegaptanib (MacugenTM) and avacincaptad pegol (IzervayTM), both for the treatment of age-related macular degeneration (AMD). Targeting vascular endothelial growth factor (VEGF), which plays an important role in the pathogenesis of many eye diseases, pegaptanib emerged as the first anti-VEGF agent and was used in various indications, further inspiring the development of other anti-VEGF therapies. In this review, we summarize the history of the first approved aptamer medicine, pegaptanib. We describe its chemistry and track its development from the earliest stages to the preclinical phase, clinical trials, and eventual regulatory approval. Additionally, we evaluate its position among other therapeutic agents and provide a comprehensive overview of pegaptanib's efficacy, safety, and cost-effectiveness, comparing these aspects with those of monoclonal antibodies with similar indications, bevacizumab and ranibizumab.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Silver Nanoclusters to Combat <i>Staphylococcus aureus</i> in the Era of Antibiotic Resistance.","authors":"Julieta Chiappero, Gustavo A Monti, Diego F Acevedo, Natalia S Paulucci, Edith I Yslas","doi":"10.3390/pharmaceutics17030393","DOIUrl":"10.3390/pharmaceutics17030393","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In the race to develop new antibiotics to combat multidrug-resistant bacteria, particularly the <i>ESKAPE</i> pathogens which pose a significant threat to public health, silver nanoclusters (AgNCs) have emerged as a promising alternative. This article focuses on the potential of novel silver nanoclusters as an antimicrobial agent against <i>Staphylococcus aureus</i>, a high-priority pathogen known for its ability to cause persistent nosocomial infections and develop protective biofilms. <b>Methods</b>: In this study, we successfully synthesized AgNCs at pH 7 using an eco-friendly photoreduction method with poly acrylic acid (PAA) and poly methacrylic acid (PMAA) as stabilizers. This methodology produced fluorescent AgNCs, demonstrating their stability in aqueous solutions for at least three months and highlighting the effectiveness of PAA and PMAA as stabilizing agents. The AgNCs were incubated with <i>S. aureus</i> suspension, and the antimicrobial capability at different concentrations and times of incubation were determined. Also, the AgNCs hemocompatibility was studied by exposing the clusters to rat blood cells. <b>Results</b>: The in vitro assays revealed that AgNCs capping with PAA or PMAA has antimicrobial activity in low doses (the determination of minimum inhibitory concentration (MIC): 0.2 µg/mL, and the determination of minimum bactericidal concentration (MBC): 2 µg/mL) and without cytotoxicity (hemolysis less than 10%) to rat blood cells until 1 µg/mL. In the presence of both AgNCs (5 µg/mL), bacterial growth was completely inhibited within just 3 h. <b>Conclusions:</b> The findings of this study highlight the potential of silver nanoclusters as effective antimicrobial agents against <i>S. aureus</i>. Their stability, low toxicity, and rapid bactericidal activity make them promising candidates for further development in antimicrobial applications.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Medicine: How 3D Printing Is Transforming Pharmaceuticals.","authors":"Jurga Bernatoniene, Jolita Stabrauskiene, Jurga Andreja Kazlauskaite, Urte Bernatonyte, Dalia Marija Kopustinskiene","doi":"10.3390/pharmaceutics17030390","DOIUrl":"10.3390/pharmaceutics17030390","url":null,"abstract":"<p><p>Three-dimensional printing technology is transforming pharmaceutical manufacturing by shifting from conventional mass production to additive manufacturing, with a strong emphasis on personalized medicine. The integration of bioinks and AI-driven optimization is further enhancing this innovation, enabling drug production with precise dosages, tailored drug-release profiles, and unique multi-drug combinations that respond to individual patient needs. This advancement is significantly impacting healthcare by accelerating drug development, encouraging innovative pharmaceutical designs, and enhancing treatment efficacy. Traditional pharmaceutical manufacturing follows a one-size-fits-all approach, which often fails to meet the specific requirements of patients with unique medical conditions. In contrast, 3D printing, coupled with bioink formulations, allows for on-demand drug production, reducing dependency on large-scale manufacturing and storage. AI-powered design and process optimization further refine dosage forms, printability, and drug release mechanisms, ensuring precision and efficiency in drug manufacturing. These advancements have the potential to lower overall healthcare costs while improving patient adherence to medication regimens. This review explores the potential, challenges, and environmental benefits of 3D pharmaceutical printing, positioning it as a key driver of next-generation personalized medicine.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-Based Therapies for Preventing Post-Surgical Adhesions.","authors":"Zi Yi Teo, Samyuktha Dhanalakshmi Senthilkumar, Dinesh Kumar Srinivasan","doi":"10.3390/pharmaceutics17030389","DOIUrl":"10.3390/pharmaceutics17030389","url":null,"abstract":"<p><p>Adhesions are the body's natural response to various inflammatory causes, with surgery being the most common cause. However, the formation of postoperative adhesions can lead to significant complications, including intestinal obstruction and chronic pain. To prevent such postoperative complications associated with adhesions, developing effective strategies for adhesion prevention has been a major focus of research. Currently, several therapeutic models have been developed to achieve this objective. These include pharmaceuticals, inert polymers, functional biomaterials, and nanotherapeutics. Among the various strategies developed, nanotherapeutics, though still in its early stages, has shown promise as a potential approach. Other therapeutic models are associated with adverse side effects and complications related to their application. On the other hand, nanotherapeutic models are able to overcome the limitations of the other strategies and provide their own set of unique advantages. Hence, nanotherapeutics represents a promising area for further research. Further efforts should be made to refine existing nanotherapeutics for clinical application while also addressing associated safety and ethical concerns related to their use in medical practice. Therefore, this article aims to review the various nanotherapeutic approaches developed for the prevention of postoperative adhesions, explore their regulatory pathways, and discuss associated safety and ethical concerns.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in Gene Therapy for Hereditary Tyrosinemia Type 1.","authors":"Helen Thomas, Robert C Carlisle","doi":"10.3390/pharmaceutics17030387","DOIUrl":"10.3390/pharmaceutics17030387","url":null,"abstract":"<p><p>Hereditary Tyrosinemia Type-1 (HT1), an inherited error of metabolism caused by a mutation in the fumarylacetoacetate hydrolase gene, is associated with liver disease, severe morbidity, and early mortality. The use of NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione) has almost eradicated the acute HT1 symptoms and childhood mortality. However, patient outcomes remain unsatisfactory due to the neurocognitive effects of NTBC and the requirement for a strict low-protein diet. Gene therapy (GT) offers a potential single-dose cure for HT1, and there is now abundant preclinical data showing how a range of vector-nucleotide payload combinations could be used with curative intent, rather than continued reliance on amelioration. Unfortunately, there have been no HT1-directed clinical trials reported, and so it is unclear which promising pre-clinical approach has the greatest chance of successful translation. Here, to fill this knowledge gap, available HT1 preclinical data and available clinical trial data pertaining to liver-directed GT for other diseases are reviewed. The aim is to establish which vector-payload combination has the most potential as a one-dose HT1 cure. Analysis provides a strong case for progressing lentiviral-based approaches into clinical trials. However, other vector-payload combinations may be more scientifically and commercially viable, but these options require additional investigation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Neuroinflammation in Central Nervous System Diseases by Oral Delivery of Lipid Nanoparticles.","authors":"Yuan Zou, Jing Zhang, Longmin Chen, Qianqian Xu, Sheng Yao, Hong Chen","doi":"10.3390/pharmaceutics17030388","DOIUrl":"10.3390/pharmaceutics17030388","url":null,"abstract":"<p><p>Neuroinflammation within the central nervous system (CNS) is a primary characteristic of CNS diseases, such as Parkinson's disease, Alzheimer's disease (AD), amyotrophic lateral sclerosis, and mental disorders. The excessive activation of immune cells results in the massive release of pro-inflammatory cytokines, which subsequently induce neuronal death and accelerate the progression of neurodegeneration. Therefore, mitigating excessive neuroinflammation has emerged as a promising strategy for the treatment of CNS diseases. Despite advancements in drug discovery and the development of novel therapeutics, the effective delivery of these agents to the CNS remains a serious challenge due to the restrictive nature of the blood-brain barrier (BBB). This underscores the need to develop a novel drug delivery system. Recent studies have identified oral lipid nanoparticles (LNPs) as a promising approach to efficiently deliver drugs across the BBB and treat neurological diseases. This review aims to comprehensively summarize the recent advancements in the development of LNPs designed for the controlled delivery and therapeutic modulation of CNS diseases through oral administration. Furthermore, this review addresses the mechanisms by which these LNPs overcome biological barriers and evaluate their clinical implications and therapeutic efficacy in the context of oral drug delivery systems. Specifically, it focuses on LNP formulations that facilitate oral administration, exploring their potential to enhance bioavailability, improve targeting precision, and alleviate or manage the symptoms associated with a range of CNS diseases.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Liposomal Interleukin and Liposomal Interleukin Gene Therapy for Cancer: A Comprehensive Review of Preclinical Studies.","authors":"Eman A Kubbara, Ahmed Bolad, Husam Malibary","doi":"10.3390/pharmaceutics17030383","DOIUrl":"10.3390/pharmaceutics17030383","url":null,"abstract":"<p><strong>Background: </strong>Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies.</p><p><strong>Methods: </strong>A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: (\"liposomal interleukin\" OR \"liposome-encapsulated interleukin\") AND (\"gene therapy\" OR \"gene delivery\") AND (\"cancer\" OR \"tumor\" OR \"oncology\") AND (\"pre-clinical studies\" OR \"animal models\" OR \"in vitro studies\".</p><p><strong>Results: </strong>Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35-50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes.</p><p><strong>Conclusions: </strong>Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}