AAPS PharmSciTech最新文献

{"title":"Dasatinib Pharmacokinetics and Advanced Nanocarrier Strategies: from Systemic Limitations to Targeted Success","authors":"Mahesha Keerikkadu,&nbsp;Pragathi Devanand Bangera,&nbsp;Vamshi Krishna Tippavajhala,&nbsp;Mahalaxmi Rathnanand","doi":"10.1208/s12249-025-03130-7","DOIUrl":"10.1208/s12249-025-03130-7","url":null,"abstract":"<div><p>Dasatinib (DSB) is a second-generation tyrosine kinase inhibitor widely used for treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Though clinically effective, DSB has some pharmacokinetic drawbacks evidenced by rapid systemic clearance, low oral bioavailability, and poor aqueous solubility requiring high doses for therapeutic action. Novel formulation strategies like solid dispersions, liposomal formulations, and PEGylated and hybrid nanoparticles enhance DSB's pharmacokinetic and pharmacodynamic profiles by enhancing drug solubility, stability, and controlled release. In addition, through these targeted drug-delivery systems based on ligand-functionalized nanoparticles and antibody–drug conjugates-the tumor-targeted DSB is allowed selective accumulation at the tumor site, causing fewer off-target effects and lessening systemic toxicity while maximizing effectiveness. These approaches are geared toward utilizing nanotechnology to improve intracellular drug uptake and extend the circulation time to optimize antitumor efficacy. Overall, those advances in drug delivery systems could greatly boost the therapeutic efficacy of DSB by providing better bioavailability, controlled release, and targeted distribution. Such advances would increase treatment success in CML and Ph + ALL and expand DSB's potential clinical applications toward other malignancies. Research concerning the delivery of DSB with nanocarriers and ligand-mediated targeting strategies should bear further fruits to augment DSB therapy in oncology.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03130-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Electrosprayed Janus Particles for Combined Photo-Chemotherapy","authors":"Brenda Sanchez-Vazquez,&nbsp;Adérito J. R. Amaral,&nbsp;Deng-Guang Yu,&nbsp;George Pasparakis,&nbsp;Gareth R. Williams","doi":"10.1208/s12249-025-03137-0","DOIUrl":"10.1208/s12249-025-03137-0","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944293","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":"AG86 Peptide-modified Reactive Oxygen Species-responsive Polymer Nanovesicles for Transdermal Delivery of Hydrophilic Ergothioneine to Basal Keratinocytes","authors":"Junlong Chen,&nbsp;Yiqing Long,&nbsp;Xiaozeliang Zhou,&nbsp;Zongning Yin","doi":"10.1208/s12249-025-03122-7","DOIUrl":"10.1208/s12249-025-03122-7","url":null,"abstract":"<div><p>This study aims to develop a multifunctional polymer nanovesicle system, AG86-β-glucan-poly(methionine-b-carboxybetaine) (AGPMC), which integrates AG86 peptide (a targeting ligand for the α6β4 integrin on basal keratinocytes) and reactive oxygen species (ROS) responsiveness to enhance the transdermal delivery of ergothioneine (EGT). The objective is to overcome the limitations of hydrophilic drug delivery and provide a targeted, ROS-triggered strategy for treating skin lipofuscin. AGPMC was synthesized via RAFT and ROP polymerization and self-assembles into stable nanovesicles (ANVs). Physicochemical characterization confirmed that the unloaded ANVs have an average size of 106.17 ± 3.26 nm and a polydispersity index (PDI) of 0.261 ± 0.027, with excellent stability and clear ROS-triggered structural responsiveness. After EGT loading, the nanovesicles exhibited a size of 140.10 ± 3.33 nm and a PDI of 0.217 ± 0.008. <i>In vitro</i> studies using HaCaT cells demonstrated a significant enhancement in cellular uptake, with an increase of up to 2.2-fold compared to free FSS (<i>p</i> &lt; 0.0001), as well as effective ROS scavenging and minimal cytotoxicity. The endocytosis mechanism study revealed that ANVs are primarily taken up via energy-dependent active transport, with caveolae-mediated endocytosis being the main pathway. Moreover, transdermal delivery studies confirmed that EGT-loaded nanovesicles significantly improved drug penetration through the stratum corneum. This work represents the first application of the AG86-conjugated nanovesicles for keratinocyte-targeted delivery, combined with ROS responsiveness. The “Loading-Targeting-Responding “ strategy holds significant potential for enhancing hydrophilic drug delivery and offers a promising approach for treating age-related skin lipofuscin accumulation.</p><h3>Graphical Abstract</h3><p>Targeted delivery of EGT via the “Loading-Targeting-Responding” strategy.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925676","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":"Oleogel-mediated Topical Administration of Roflumilast and Paclitaxel as a Synergistic Strategy to Combat Imiquimod-induced Psoriasis","authors":"Wenxiu Pan,&nbsp;Yunyi Shi,&nbsp;Fei Sun,&nbsp;Meijuan Zou,&nbsp;Hongyu Piao","doi":"10.1208/s12249-025-03118-3","DOIUrl":"10.1208/s12249-025-03118-3","url":null,"abstract":"<div><p>Psoriasis is a systemic immune disease with severe inflammation and skin thickening. Roflumilast (ROF) blocks cAMP hydrolysis, and paclitaxel (PTX) inhibits cell proliferation; both are effective in topical psoriasis treatment. However, the combination of ROF and PTX has not been reported. This study explored their synergistic mechanism and formulated a ROF-PTX oleogel with strong skin adhesion, low viscosity, enhanced skin penetration, and increased retention. The oleogel, prepared via direct gelation with jojoba oil as oil phase, PPG-15 as solvent, Transcutol as solubilizer, and hydrogenated castor oil as oleogelator. It showed 78.9% holding oil capacity and a viscosity of 0.4049 Pa·s, indicating excellent stability and adhesion. In the imiquimod-induced psoriasis model, the ROF:PTX (1:1) oleogel reduced Baker scores and splenic indices more effectively than ROF or PTX alone. Histological studies suggested that the combination was superior in reducing inflammation and skin thickening. The ROF:PTX (1:1) oleogel group exhibited lower Baker scores and epidermal thickness, demonstrating superior therapeutic efficacy. The H-SCORE revealed a 2.95-fold reduction in IL-17 levels compared to the model group, highlighting the potential of the ROF and PTX combination as an effective psoriasis treatment strategy.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925630","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":"Leveraging Nanoscience and Strategic Delivery for the Expedition of Osteoporosis","authors":"Pramoda G,&nbsp;Rahul K. Verma,&nbsp;Rahul Shukla","doi":"10.1208/s12249-025-03120-9","DOIUrl":"10.1208/s12249-025-03120-9","url":null,"abstract":"<div><p>Osteoporosis is a globally affecting bone disease characterized by reduced bone mineral density, in which women are more insidious to the disease. It accounts for 8.9 million fractures annually, and about 50% of repeated hip fractures cause permanent disabilities. With the knowledge of determinants and pathology, various FDA-approved drugs and therapies are available for the management of the disease, but the challenges associated with those therapies lead to the adoption of nanotechnology in osteoporosis management. The nanosystems developed for the management of osteoporosis are nanogenerators, nanobubbles, microneedles, nanogels, implantable delivery systems, nanoparticles, nanofibrous scaffolds, and nanocements that probably address the current challenges related to the diagnosis and cure. In view of targeted accumulation of the cargo, various moieties assisted the nanocarrier system for selective distribution to bone, and the development of different types of nanotechnology-based delivery systems has been briefed in this review.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925675","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":"Development and Characterization of Chitosan Nanoparticles Containing Quercetin-β-Cyclodextrin Inclusion Complex for Improved Solubility, Brain Targeting, and Neuroprotective Potential Against Epilepsy","authors":"Priyabrata Pradhan,&nbsp;Vineet Kumar Rai,&nbsp;Jitu Halder,&nbsp;Durgamadhab Kar,&nbsp;Shakti Ketan Prusty,&nbsp;Saroj Kumar Rout,&nbsp;Salim Manoharadas,&nbsp;Subramanian Palanisamy,&nbsp;Priyanka Dash,&nbsp;Chandan Das,&nbsp;Biswakanth Kar,&nbsp;Goutam Ghosh,&nbsp;Goutam Rath","doi":"10.1208/s12249-025-03119-2","DOIUrl":"10.1208/s12249-025-03119-2","url":null,"abstract":"<div><p>The present study focuses on developing and optimising chitosan nanoparticles containing quercetin-β-cyclodextrin inclusion complex (QNPs) using the nanoprecipitation method to enhance quercetin's solubility, stability, and bioavailability. A comprehensive optimization study revealed that Batch B6, which utilized ethanol as the solvent, poloxamer 188 as the stabilizer, and chitosan at a concentration of 0.2% (w/v), exhibits optimal characteristics required for providing a stable colloidal system. The prepared nanoparticles were characterized for their physicochemical properties using FTIR, DSC, X-ray Diffraction, and SEM, which confirmed the successful inclusion of quercetin within the β-cyclodextrin complex and the reduction in crystallinity. <i>In-vitro</i> drug release studies demonstrated a controlled release profile for QNPs compared to free quercetin and the inclusion complex. Pharmacokinetic evaluation in mice via oral administration revealed a significant enhancement in systemic circulation and brain uptake, with QNPs showing a peak plasma concentration of 6.5 µg/mL at 2 h and a brain concentration of 3.5 µg/g at 4 h, indicating improved bioavailability and prolonged retention. In the Pentylenetetrazole and Kainic acid-induced epilepsy mice model, QNP significantly reduced seizure duration, frequency of seizures, and severity scores favoured the QNP formulation over free quercetin. QNPs also exhibited a significant neuroprotective effect by enhancing antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione reductase in brain tissue. Furthermore, Na⁺/K⁺-ATPase activity was significantly preserved in QNP-treated groups, indicating membrane stability and reduced neuronal excitability. These findings suggest that QNPs offer a promising strategy for enhancing quercetin's therapeutic efficacy in neurological disorders such as epilepsy.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913838","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":"Design, Development, and Characterization of High Drug-Loaded Drug-Drug-Polymer Ternary Amorphous Solid Dispersions","authors":"Sagar Kumar Paul,&nbsp;Dunesh Kumari,&nbsp;Joel Destino,&nbsp;Harsh Chauhan","doi":"10.1208/s12249-025-03123-6","DOIUrl":"10.1208/s12249-025-03123-6","url":null,"abstract":"<div><p>Ternary amorphous solid dispersions (TASD) are a three-component system that incorporates at least one drug in an amorphous form, offering potential advantages over conventional binary amorphous solid dispersions (ASD). This study aimed to design, characterize, and evaluate a stable and soluble high drug-loaded TASD combining two poorly water-soluble drugs, curcumin (CUR) and resveratrol (RES), with a hydrophilic polymer. Polymer screening studies, including miscibility, crystallization tendency, Flory–Huggins interaction parameter, and solubility parameter, were complemented by advanced techniques such as crystallization kinetics and molecular interaction analysis to assess drug-polymer interactions and amorphous stability. After selecting the optimal polymer, TASDs were prepared by rotary evaporation. Pure drugs, physical mixtures, binary, and ternary ASDs were characterized using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy, and Raman spectroscopy. <i>In-vitro</i> dissolution under non-sink conditions was performed using a USP-II apparatus, and centrifuged samples were analyzed by UV–Vis spectroscopy. Long-term physical stability was assessed over 12 months at room temperature. Eudragit EPO was identified as the optimal polymer among EPO, HPMCAS, and S100. The resulting high drug-loaded (50% w/w) TASD was amorphous, exhibiting a single glass transition temperature (Tg) with strong drug-polymer interactions. In dissolution studies, the 50% drug-loaded TASD showed a ~ 197-fold and ~ fourfold increase in dissolved CUR and RES, respectively, compared to the crystalline drugs in the physical mixture after 1 h in acidic condition. Despite a lower RES release, it was still twice the release from binary ASDs. The TASD formulation remained physically amorphous for 12 months at room temperature storage.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913784","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":"Ethyl-Cellulose Nanosponges for Topical Delivery of Simvastatin with Preferential Skin Retention for Wound Healing in a Full-Thickness Wound Rat Model","authors":"Samar Aboelazayem,&nbsp;Maha Nasra,&nbsp;Heba Ebada,&nbsp;Ossama Abdallah","doi":"10.1208/s12249-025-03114-7","DOIUrl":"10.1208/s12249-025-03114-7","url":null,"abstract":"<div><p>Novel topical nanosponges were implemented to improve the skin availability of simvastatin (SV) for treating full-thickness wounds while controlling the scarring process. SV exhibits great potential in treating various skin diseases owing to its antibacterial, antioxidant, anti-inflammatory, and immunomodulatory properties. However, its poor oral bioavailability and systemic side effects have hindered its clinical application in dermatology. For the first time, nanosponges were utilized to target injured skin, creating an SV reservoir within the wound bed to enhance therapeutic efficacy while minimizing adverse effects. Herein, SV-loaded ethyl-cellulose nanosponges (SV-NS) were prepared using the emulsion solvent evaporation technique, optimizing organic solvents, SV concentration, and stabilizer concentration. The selected SV-NS (20 mg SV) exhibited nanoporous particles (786.2 ± 50 nm), a specific surface area of 10.3 m²/g, and a total pore volume of 0.016 cm³/g, offering sustained release and enhanced skin retention capacity. <i>In vivo</i> studies on full-thickness rat wounds confirmed that topical SV-NS (5 mg SV, applied every 5 days) significantly accelerated wound closure (<i>P</i> &lt; 0.0001), achieving 76.23 ± 3.20% closure by day 8, a 47% improvement over free SV. Consequently, SV-NS facilitated wound closure exceeding 90% by day 11, whereas free SV required 16 days to attain a comparable level, representing a 31.2% faster healing rate. Histological analysis further revealed that SV-NS promoted optimal epidermal layer formation and well-organized collagen deposition, with collagen expression significantly (<i>P</i> &lt; 0.0001) reaching 59.85 ± 3.17% by day 16. Conclusively, SV-NS enhances SV’s dermal availability, improving wound healing and minimizing side effects, demonstrating a promising approach for wound restoration.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03114-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a Two-Phase Experiment Design and Optimization Method to Formulate Ciprofloxacin-Loaded Bovine Serum Albumin Nanoparticles with High-Entrapment Efficiency for Targeting Urinary Tract Infections","authors":"Sofía V. Sánchez,&nbsp;Erlen Cruz Jorge,&nbsp;Nicolás Navarro M.,&nbsp;María José González,&nbsp;Ricardo Vásquez,&nbsp;Felipe Del Canto,&nbsp;Paola Scavone,&nbsp;Eva C. Arrúa,&nbsp;Javier O. Morales","doi":"10.1208/s12249-025-03115-6","DOIUrl":"10.1208/s12249-025-03115-6","url":null,"abstract":"<div><p>Urinary tract infections (UTIs), predominantly caused by uropathogenic <i>Escherichia coli</i> (UPEC), pose a global health concern due to rising antibiotic resistance and biofilm formation. Albumin nanoparticles (NPs) offer a promising strategy for UTI treatment, with site-specific selectivity, improved bioavailability, and sustained drug release. This study focused on developing an optimized method for formulating ciprofloxacin-loaded albumin nanoparticles (CPF-loaded BSA NPs) to treat UPEC and its biofilms effectively. A desolvation method was used to synthesize the nanoparticles, and a two-phase experimental design was used for optimization. Evaluation parameters included size, polydispersity index, zeta potential, morphology, encapsulation efficiency, drug release, storage stability, cytotoxicity, and effectiveness against UPEC. The optimized CPF-loaded BSA NPs exhibited desirable characteristics such as small particle size (123 nm), low polydispersity index (0.178), optimum zeta potential (-31.8), and high encapsulation efficiency (&gt; 80%). They also exhibited low cytotoxicity, high stability, and sustained drug release, making them an ideal drug delivery system. Critically, they demonstrated effectiveness against UPEC and its biofilm. This study suggests that the optimized CPF-loaded BSA NPs, synthesized using our optimized desolvation technique, hold the potential for effectively treating UTIs caused by UPEC.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900666","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":"Enhancing Intracellular Uptake of Ivermectin through Liposomal Encapsulation","authors":"Meryem Kocas,&nbsp;Fumiyoshi Yamashita,&nbsp;Tansel Comoglu,&nbsp;Qiyue Zhang","doi":"10.1208/s12249-025-03113-8","DOIUrl":"10.1208/s12249-025-03113-8","url":null,"abstract":"<div><p>Ivermectin (IVM), an antiparasitic drug approved by the Food and Drug Administration (FDA), is widely used to treat several neglected tropical diseases, including onchocerciasis, helminthiases, and scabies. Additionally, IVM has shown potential as a potent inhibitor of certain RNA viruses, such as SARS-CoV-2. However, IVM is highly hydrophobic, essentially insoluble in water, which limits its bioavailability and therapeutic effectiveness. The use of liposomes as drug carriers offers several advantages, including enhanced solubility for lipophilic drugs, passive targeting of immune system cells, sustained release, and improved tissue penetration. To address the limitations of IVM, including its poor solubility and bioavailability, liposomal formulations were developed using a combination of soyphosphatidylcholine (SPC), dioleylphosphatidylcholine (DOPC), cholesterol (Ch), and diethylphosphate (DCP) in two distinct molar ratios (1.85:1:0.15 and 7:2:1) via the ethanol injection method. The physicochemical properties of the placebo and IVM-loaded liposomes were extensively characterized in our earlier study, including the particle size, polydispersity index, and zeta potential. The present work adds a deeper level of investigation into how to effect cellular uptake and cytotoxicity <i>in vitro</i> of both free IVM and IVM-loaded liposomes in Vero E6 cells. The half-maximal cytotoxic concentrations (CC₅₀) for free IVM and IVM-loaded liposomes were 10 μM and &gt; 110 μM, respectively and the cellular uptake of IVM-loaded liposomes ranged from 13 to 60%, whereas free IVM showed a significantly lower uptake of only 2%. These results demonstrate that liposomal encapsulation effectively enhances IVM’s cellular uptake while reducing its cytotoxicity, thus offering a promising strategy for improving the effectiveness of IVM.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03113-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}