Journal of Drug Delivery Science and Technology最新文献

{"title":"Ca2+ delivery into cell suspension and spheroid models via ultrasound-induced inertial cavitation","authors":"Martynas Maciulevičius ,&nbsp;Diana Ragaišė ,&nbsp;Reda Rulinskaitė ,&nbsp;Renaldas Raišutis ,&nbsp;Linas Svilainis ,&nbsp;Andrius Chaziachmetovas ,&nbsp;Kristine Saleniece ,&nbsp;Saulius Šatkauskas","doi":"10.1016/j.jddst.2025.107132","DOIUrl":"10.1016/j.jddst.2025.107132","url":null,"abstract":"<div><div>Current study explores the application of high acoustic pressure (up to 800 kPa) for cell sonoporation (SP), which exceeds conventional pressure values, associated with stable cavitation. The resultant inertial cavitation of Sonovue microbubbles, when combined with pre-administered Ca²⁺, resulted in instant cell death of resistant Chinese hamster ovary cells. Ca²⁺, administered at the concentration of 5 mM, was capable to significantly reduce the viability of mammal cells in both suspension and spheroid culture models. Cyto-lethal action of Ca²⁺ SP was observed instantly: i) after ≤15 min for cells in a suspension and ii) from day #1 for cell spheroids.</div><div>Real-time passive cavitation detection and optical monitoring of microbubble concentration have identified inertial cavitation to be a requisite for efficient Ca²⁺ SP. Although, inertial cavitation is not preferred in therapeutic applications due to uncontrolled nature, it may be exploited to induce fast cell death when combined with Ca²⁺. And, similarly to irreversible electroporation, if reasonably monitored, may become a favorable therapeutic technique for highly-metastatic malignancies. Therefore, our research also puts extensive focus on the physical aspect of cavitation control during Ca²⁺ SP. Based on the passive monitoring of side-scattered US signals, we have determined a strong (R² ≥ 0.92) and significant (p &lt; 0.001) correlation between cumulated amount of broadband noise and the level of cavitation-induced bio-effects.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107132"},"PeriodicalIF":4.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212718","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":"Folic acid-conjugated Ferulic acid-entangled Single-Walled Carbon Nanotubes: A targeted therapeutic approach for effective breast cancer treatment","authors":"Sandra Ross Olakkengil Shajan ,&nbsp;Shivaraj Kumar Walikar ,&nbsp;Nandini Markuli Sadashivappa ,&nbsp;Devaraj Hanumanthappa ,&nbsp;Basavana Gowda Hosur Dinesh ,&nbsp;Bandral Sunil Kumar ,&nbsp;Srinivas Ganjipete ,&nbsp;Selvaraj Kunjiappan ,&nbsp;Sankaranarayanan Murugesan ,&nbsp;Panneerselvam Theivendren ,&nbsp;Kumarappan Chidambaram ,&nbsp;Damodar Nayak Ammunje ,&nbsp;Parasuraman Pavadai","doi":"10.1016/j.jddst.2025.107111","DOIUrl":"10.1016/j.jddst.2025.107111","url":null,"abstract":"<div><div>Breast cancer remains one of the major causes of cancer-related deaths in the world for women, which emphasizes the need for better treatment approaches. Conventional therapies target both cancerous as well as normal cells, which can lead to serious adverse effects. This research aimed to develop a targeted therapy employing a new folic acid-conjugated Ferulic Acid-Entangled Single-Walled Carbon Nanotubes (FA-FeA-SWCNTs) formulation to maximize treatment specificity and reduce off-target effects. The efficiency of the FA-FeA-SWCNTs formulation against breast cancer is assessed in this study. Molecular modelling studies were performed to predict the mechanism of action of ferulic acid. FA-FeA-SWCNTs particle size analysis, FTIR, XRD, and SEM were assessed to confirm the formulation tethered to single-walled carbon nanotubes (SWCNTs). MTT assay against MCF-7 cells and CAM assays in chicken eggs were executed to measure cytotoxicity and evaluate anti-angiogenesis efficacy. Sub-acute oral toxicity by OECD 407 guidelines and DMBA-induced breast cancer models in female Wistar rats were used to examine the <em>in vivo</em> anticancer efficacy. The potential therapeutic mechanism was suggested by the study's finding that the Ferulic Acid strongly interacted with mitogen-activated protein kinase (MAPK). The formulation showed excellent-, stability, and suitable particle size. Through <em>in vitro</em> tests, substantial anti-angiogenic effects (71.2 % inhibition) and significant cytotoxicity (IC₅₀ of 19.60 μg/mL) were identified. Subacute toxicity tests verified a favorable safety profile, and <em>in vivo</em>, the formulation successfully decreased tumor growth and improved overall wellness, making it a viable option for more clinical investigation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107111"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220883","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":"Nose-to-brain delivery of chitosan coated Leciplex containing zopiclone for improved management of epilepsy: Formulation, pharmacokinetics, and Pharmacodynamics","authors":"Hussein M. Eid ,&nbsp;Rahma A. Sadek ,&nbsp;Adel A. Ali ,&nbsp;Fatma I. Abo El-Ela ,&nbsp;Hanan O. Farouk","doi":"10.1016/j.jddst.2025.107078","DOIUrl":"10.1016/j.jddst.2025.107078","url":null,"abstract":"<div><div>This study focused on designing and optimizing zopiclone-loaded chitosan-coated Leciplex (ZP-CTS-LPX) to improve nose-to-brain delivery for enhanced management of epilepsy. The ZP-CTS-LPX was produced through a one-step manufacturing process, optimized via central composite design to achieve maximum entrapment, zeta potential, and minimal size. The optimized ZP-CTS-LPX underwent <em>in vitro</em> characterization and was subjected to <em>in vivo</em> evaluation studies. The results showed that the ZP-CTS-LPX formulation had a size of 145.40 nm, a surface charge of (+) 62.00 mV, and an entrapment of 68.34 %. The morphological analysis revealed that nanoparticles were spherical and displayed a uniform size distribution, free from aggregation. The research indicated improved <em>ex vivo</em> nasal diffusion, a prolonged release profile, and stability under the tested conditions. ZP-CTS-LPX (IN) demonstrated a relative bioavailability of 269 % in plasma and 690 % in the brain in comparison to ZP-SOL (IN). Furthermore, the ZP-CTS-LPX (IN) demonstrated the highest DTE% (383) and DTP% (73.95) when compared to the ZP-SOL (IN) formulation. Pharmacodynamic assessments showed that the ZP-CTS-LPX group had the longest latency and highest protection percentages against strychnine-induced seizures compared to control and standard treatments. Antioxidant investigations indicated lower oxidative stress and higher glutathione levels in treated groups, while histological analysis confirmed the safety of ZP-CTS-LPX for nasal and brain tissues. These results, coupled with superior pharmacological outcomes and reduced convulsions, demonstrate ZP-CTS-LPX as an effective and safe approach for epilepsy treatment, warranting further clinical evaluation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107078"},"PeriodicalIF":4.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220882","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":"Solid lipid discs from water-in-oil emulsion as controlled release delivery systems of highly soluble drugs","authors":"A. Candiani ,&nbsp;A. Milanesi ,&nbsp;G. Diana ,&nbsp;F. Loda ,&nbsp;E. Bari ,&nbsp;M.L. Torre ,&nbsp;A. Foglio Bonda ,&nbsp;L. Segale ,&nbsp;L. Giovannelli","doi":"10.1016/j.jddst.2025.107127","DOIUrl":"10.1016/j.jddst.2025.107127","url":null,"abstract":"<div><div>Solid lipid systems (SLSs) are widely employed to control the release of highly hydrophilic drugs, and they are, in general, obtained by solubilizing or suspending the drug within melted lipid excipients. This work proposes an advantageous strategy to modulate the drug release of a hydrophilic drug loaded into a lipid matrix using as a starting formulation a water-in-oil emulsion. Therefore, the active ingredient (metoclopramide HCl as a drug model) is solubilized in the emulsion internal phase, and some formulation and process parameters were used as variables for drug release kinetics modulation. Four lipid excipients with different chain lengths of the fatty acids (Dynasan® 114, 116, 118 and Softisan® 154) were selected as external phases by melting them and emulsifying two predefined volumes of 50 % (w/w) metoclopramide HCl aqueous solution to obtain two different drug loadings. Sixteen batches of solid lipid discs were produced by dripping each emulsion into plastic molds and solidifying in an ice bath or at room temperature. The solid lipid discs were compact after the extraction from molds and homogeneous in shape and size. The maximum percentage of residual water in the discs did not exceed 6 %, and their experimental drug content was close to the expected theoretical values. Results indicate that the drug release from the discs can be modulated by changing the percentage of the loaded drug, the length of the fatty acid chain, and the solidification conditions (room temperature or ice). This approach provides a straightforward and exploitable tool for developing other types of SLSs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107127"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212280","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":"Progress and prospects of synthetic antimicrobial polymers for the treatment of infectious diseases","authors":"Trinankita Pal ,&nbsp;Bijaya Ghosh ,&nbsp;Kaushik Mukherjee ,&nbsp;Tapan Kumar Giri","doi":"10.1016/j.jddst.2025.107126","DOIUrl":"10.1016/j.jddst.2025.107126","url":null,"abstract":"<div><div>The dreaded bacterial diseases like meningitis, pneumonia, and tuberculosis are seeing a resurgence thanks to the development of antibiotic resistance. The precious antibiotics have been rendered ineffective due to their indiscriminate and widespread application. An innovative therapeutic solution is the need of the hour. As an answer to this demand, synthetic antimicrobial polymers (SAP) have surfaced as a viable alternative. Unlike natural products, the properties of SAP can be controlled by design. Wide-spread research using various approaches has created a plethora of SAP with customizable properties like broad-spectrum antimicrobial activity, low toxicity, and a high barrier to resistance, which could play a significant role in reducing reliance on traditional antibiotics. However, a summary of this progress is unavailable, and this article tries to fill the gaps. This review explores the current state of these polymers, emphasizing their mechanisms of action as well as their efficacy and offering insights into how these materials could transform the treatment of infectious diseases.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107126"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204677","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":"Biomimetic hybrid vesicles for colorectal cancer targeting","authors":"Alice Balboni ,&nbsp;Giorgia Ailuno ,&nbsp;Mathieu Repellin ,&nbsp;Giuseppina Catania ,&nbsp;Sara Baldassari ,&nbsp;Andrea Petretto ,&nbsp;Pierre Yves Dugas ,&nbsp;Cédric Chaveroux ,&nbsp;Gabriele Caviglioli ,&nbsp;Giovanna Lollo","doi":"10.1016/j.jddst.2025.107124","DOIUrl":"10.1016/j.jddst.2025.107124","url":null,"abstract":"<div><div>The functionalization of nanosystems with cell-derived materials has been proposed as a promising strategy for targeted drug delivery. This approach combines high colloidal stability and low rate of clearance from the reticuloendothelial system, with a controlled preparation process. In this work, colorectal cancer cells from a murine cell line (CT26 cells) were used as cell membrane (CM) source for the preparation of biomimetic nanosystems intended for cancer cells targeting. The purification from residual genetic material from parent cells was assessed in the CM fraction and the retained protein profile was studied. CT26 CM were used to prepare vesicles, and combined with synthetic lipids at different protein:lipid ratios to obtain hybrids. CM and lipids were hybridized using two techniques: co-extrusion and hydrodynamic mixing using microfluidics. The obtained formulations were compared in terms of physicochemical properties, protein content and membrane hybridization. The insertion of artificial phospholipids in hybrid vesicles enabled to improve the production yield. The internalization and selectivity of biomimetic vesicles into parent cells compared to different cell types was assessed <em>in vitro</em>, likewise their biocompatibility in 2D and 3D cell cultures. The obtained results demonstrated that purified and stable bio-inspired nanosystems were developed with high throughput, evidencing the superiority of microfluidics in terms of material conservation and process standardization. Moreover, significantly improved cellular uptake of the developed systems was observed when compared to artificial liposomes, reaching the highest value in the homotypic internalization to parent cells.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107124"},"PeriodicalIF":4.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212279","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":"Enhanced semaglutide bioavailability via spray freeze dried powder for inhalation: Unveiling safety and broad potential applications","authors":"Riwei Yang ,&nbsp;Kaiqi Shi ,&nbsp;Qingzhen Zhang ,&nbsp;Gang Yang ,&nbsp;Shiyang Liu ,&nbsp;Shuo Qi ,&nbsp;Xiang Luo ,&nbsp;Honglei Zhang ,&nbsp;Zheng Wang ,&nbsp;Fangyan Wang ,&nbsp;Jesse Zhu","doi":"10.1016/j.jddst.2025.107112","DOIUrl":"10.1016/j.jddst.2025.107112","url":null,"abstract":"<div><div>Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, has been approved for blood glucose management in Type 2 diabetes (T2D) and obese patients. However, its clinical use is limited by poor oral bioavailability and suboptimal adherence to subcutaneous injections, highlighting the need for alternative delivery routes. In this study, we developed semaglutide dry powder for inhalation (sema-DPI) using spray drying (SD) and spray freeze drying (SFD) techniques, and evaluated their characteristics of particle and pharmacokinetics through modern preparation assessment methods. The results indicated that under similar parameters, SFD-sema-DPI exhibited a rougher particle surface compared to the SD-sema-DPI, which provided better aerodynamic performance. Additionally, SFD-sema showed prolonged plasma presence in rats and enhanced bioavailability. Furthermore, the inhalation safety of SFD-sema-DPI was evaluated in rats. Continuous inhalation at a dose of 4.1 mg/kg/day for 28 days did not produce any significant pulmonary or systemic lesions. Our findings suggest that SFD-sema-DPI may offer a superior alternative for T2D and obese patients.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107112"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204679","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":"Engineering elastin-like polypeptides for polyphenol capture and permeation through an in vitro nasal mucosa barrier","authors":"Derek W. Nelson ,&nbsp;Gianna M. Scire ,&nbsp;Conrad H. Cheung ,&nbsp;Vrushali Varude ,&nbsp;Geraldine Quinones ,&nbsp;Marvin Bentley ,&nbsp;R. Helen Zha ,&nbsp;Ryan J. Gilbert","doi":"10.1016/j.jddst.2025.107119","DOIUrl":"10.1016/j.jddst.2025.107119","url":null,"abstract":"<div><div>Intranasal (IN) administration provides a potential drug delivery route to the brain without passing the blood-brain barrier, allowing for the delivery of larger therapeutics for diseases such as Alzheimer's disease (AD). However, effective IN administration is compromised by mucociliary clearance (MCC) and the use of complex formulations of thermo-gelling modalities to reduce MCC. This study uses biomimetic elastin-like polypeptides (ELPs) to gel at nasal passage temperatures, capture an AD-relevant polyphenol, vescalagin (VSG), and deliver VSG through a nasal mucosa model. First, a library of ELPs was produced bearing either tyrosine, phenylalanine, serine, or leucine guest residues. The phenyl-bearing ELPs elicit a physiologically relevant gelation temperature and have the best VSG drug binding, as determined by a pull-down assay. Next, a di-block ELP was produced with a tyrosine-bearing block for drug binding and phase separation and a leucine-bearing block that remains soluble and presents a polyarginine tag (10xR) for cell interaction. While the di-block ELP resulted in stable microgels compared to mono-block ELPs upon phase separation, adding the 10xR tag mitigated this stability, returning the di-block ELP to coalescence behavior. However, the 10xR tag elicited ELP interaction with RPMI cells, enhanced VSG accumulation at the cell-mucous surface of an in vitro nasal mucosa model, and increased VSG permeation compared to un-tagged ELP or VSG alone. Future work can use these findings to improve ELP design for IN applications and investigate in vivo efficacy.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107119"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220884","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":"Advances in pH-Sensitive polymer-based Drug delivery systems for targeted therapy in ovarian Cancer: Focus on Olaparib","authors":"S. Nikitha,&nbsp;D. Manjula,&nbsp;Arfa Nasrine","doi":"10.1016/j.jddst.2025.107076","DOIUrl":"10.1016/j.jddst.2025.107076","url":null,"abstract":"<div><div>With an importance on OLA(Olaparib), this review scrutinizes the developments in pH-sensitive polymer-based drug delivery systems for targeted therapy in ovarian cancer(OC). The article studies the methods of increasing bioavailability and solubility of OLA using pH-sensitive polymers compared to traditional polymers. It describes the mechanisms of conjugation of OLA, provides examples of pH-sensitive polymers, the methods of their synthesis, the ways of functionalization and modification. This review describes how this drug, when integrated with nanotechnology using this pH-sensitive polymer, offers enhanced therapeutic effects by specifically targeting OC cells while reducing the systemic toxicity towards the normal cells, which surpasses the efficacy and toxicity of traditional forms like tablets, and capsules, while explaining how this system better overcomes medication resistance than available conventional forms. The paper discusses regulatory subjects for clinical application as well as problems with polymer manufacturing, stability, and biocompatibility. Lastly, it looks at prospective future avenues, such as progressions in multi-responsive systems, precision medicine integration with nanotechnology, and possible combination therapy with OLA for synergistic effects. While identifying the need for more study to overcome current obstacles, the conclusion highlights the extensive potential of pH-sensitive polymers in enhancing the results of OC treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107076"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204678","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":"Enhancing luteolin solubility through solid dispersion-based oral gels: A novel approach for periodontal disease treatment","authors":"Maria Koromili ,&nbsp;Afroditi Kapourani ,&nbsp;Konstantina Chaclioutaki ,&nbsp;Nikoletta Christoudia ,&nbsp;Spyros Pettas ,&nbsp;Dimitra Dafou ,&nbsp;Theodoros Sklaviadis ,&nbsp;Dimitrios A. Andreadis ,&nbsp;Spyros Papageorgiou ,&nbsp;Andreana N. Assimopoulou ,&nbsp;Konstantinos Xanthopoulos ,&nbsp;Dimitrios N. Fatouros ,&nbsp;Panagiotis Barmpalexis","doi":"10.1016/j.jddst.2025.107121","DOIUrl":"10.1016/j.jddst.2025.107121","url":null,"abstract":"<div><div>Luteolin (LUT) is a bioactive flavonoid with numerous pharmacological properties, such as antioxidant, antimicrobial, and anti-cancer activity. A prominent example of LUT's properties concerns its administration for the treatment of periodontal disease. However, its low water solubility poses a serious challenge regarding its formulation into an effective dosage form. To this end, the present study investigates the incorporation of LUT's solid dispersions (SDs) into oral gels, as a way to improve LUT solubility in saliva for the treatment of periodontitis. Initially, SDs of LUT were formulated at drug-to-polymer weight ratios of 1:9 and 1:12 using either polyethylene glycol 6000 (PEG) or poloxamer P188 (P188), employing both melting and solvent evaporation techniques. Subsequently, these drug-loaded SDs were integrated into oral gels designed for the local treatment of periodontal disease within the mouth. The SDs resulted in a remarkable solubility enhancement for LUT, showing up to a 16-fold increase compared to its pure crystalline form. Physicochemical characterization using differential scanning calorimetry (DSC) and powder X-ray diffractometry (pXRD), revealed that LUT was amorphously dispersed within the SDs, while ATR-FTIR spectroscopy indicated the presence of significant molecular interactions between the drug and the matrix/carriers. The gels containing the SDs of LUT displayed appropriate rheological properties for handling and storage, while the <em>in vitro</em> dissolution studies in simulated saliva revealed that the PEG SD-based oral gels were able to significantly enhance LUT's release. Moreover, cell viability studies, which examined two promising SDs (one with PEG and one with P188), revealed negligible cytotoxicity, suggesting that the prepared formulations exhibit favorable and non-toxic characteristics. In addition, <em>in vitro</em> assays demonstrated that the formulations retained LUT's anti-inflammatory effect. Finally, <em>ex vivo</em> permeation studies using porcine buccal tissue demonstrated that P188-based SD, incorporated into a placebo gel, enhanced the ability of LUT to partition into and accumulate within the mucosal tissue, resulting in more than three-times the accumulation compared to the gel containing the neat drug. Therefore, the preparation of SD oral gels for LUT can be regarded as a prospective technique with strong potential for the improvement of the API's solubility and hence, its administration in the oral cavity for the topical treatment against periodontitis.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"111 ","pages":"Article 107121"},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204680","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}