European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Synthesis and Anticancer Activity Evaluation of Self- assembled Curcumin Loaded Gelatin − Oleic acid – Carboxymethyl Chitosan Nanoparticles on MCF-7 cells","authors":"Lekshmi Geetha Sivasankaran,&nbsp;Suriya Rahim,&nbsp;Anirudhan Thayyath Sreenivasan","doi":"10.1016/j.ejpb.2025.114718","DOIUrl":"10.1016/j.ejpb.2025.114718","url":null,"abstract":"<div><div>Curcumin (CUR) is a natural herb with known anticancer effects against many malignancies such as breast cancer. However, CUR is poorly water-soluble and suffers from low bioavailability, and its delivery to breast cancer through oral administration is interrupted by early release and degradation before reaching the target site. So, this study aimed to develop an oral breast cancer-targeted drug delivery system (DDS) using a combination of biopolymers like mucoadhesive carboxymethyl chitosan, oleic acid and gelatin to create biopolymer-mediated nanoparticles (NPs) for the delivery of hydrophobic CUR. Gelatin-Oleic acid-Carboxymethyl chitosan (GOC) readily self-assembles into nanoparticles (GOCNPs) using the desolvation process. Such self-assembled DDS based on biopolymers without any crosslinkers for the preparation present controlled drug release and enhanced anticancer efficacy compared to existing systems. The prepared GOCNPs were characterized by FTIR, ¹HNMR, XRD, SEM, HRTEM, DLS, and Zeta analysis. The DDS’s maximum drug loading efficiency (DLE) and encapsulation efficiency (EE) values at pH 4.0 were 78.0 ± 2.34 % and 94.0 ± 2.8 %, respectively. The CUR-loaded GOCNPs shows a 90.0 ± 2.6 % CUR release at pH 5.5, while the release percentage of CUR at pH 7.4 was only 37.0 ± 1.06 %. According to the MTT data, CUR-GOCNPs show significant cytotoxicity to MCF-7 cells, showed a cell viability of 20.16 % towards MCF-7 cancer cells and loading of CUR to the GOCNPs notably increased its anticancer activity as the IC50 of CUR-GOCNPs was significantly lowered (6.880 µg/mL against MCF-7 in 24 h analysis). Studies on drug release kinetics, cytotoxicity, apoptosis, hemocompatibility, swelling, and <em>in vivo</em> pharmacokinetics were carried out to prove the effectiveness of the biopolymer-based nanoparticles developed as an effective oral delivery system for CUR. The future holds enormous possibilities for the clinical translation of prepared drug delivery system, as advances in controlled drug delivery continue to prove the design and capabilities of GOCNPs.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114718"},"PeriodicalIF":4.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Release profiles prediction of diclofenac sodium patches using Raman mapping technique","authors":"Wenliang Dong ,&nbsp;Yadong Zhu ,&nbsp;Yinglian Yang ,&nbsp;Zhenhao Tang ,&nbsp;Yunfei Hu ,&nbsp;Lian Li ,&nbsp;Wenlong Li","doi":"10.1016/j.ejpb.2025.114716","DOIUrl":"10.1016/j.ejpb.2025.114716","url":null,"abstract":"<div><div><strong>Objective</strong>: To explore a rapid, nondestructive and accurate method for predicting the in vitro release profiles of transdermal system based on Raman mapping. <strong>Methods</strong>: Commercial diclofenac sodium patches of different production batches were purchased, Raman spectral data of the fixed surface area of all samples were collected and the distribution of active ingredients was visualized. Then the in vitro release of all patch samples was determined as the standard value using the method in the pharmacopeia. Then the partial least squares model and two convolutional neural network models were established to predict the in vitro release of patch samples at specific time points and the parameters of the equation fitting the in vitro release curve. Finally, the prediction accuracy of all models was evaluated. <strong>Results</strong>: All models showed excellent prediction accuracy for in vitro release fraction at specific time points. For the prediction of equation parameters, the prediction accuracy of partial least squares model is satisfactory. <strong>Conclusion</strong>: Based on Raman mapping, the establishment of models such as convolutional neural network is a fast and reliable method for characterizing the in vitro release degree of patches. It avoids many shortcomings of traditional methods and has great research potential and application value.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114716"},"PeriodicalIF":4.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles delivered rapamycin to improve the tumor microenvironment and enhance hepatocellular carcinoma immunotherapy","authors":"Jihua Tian ,&nbsp;Huanyu Xu ,&nbsp;Zhijie Ma ,&nbsp;Jing Wang ,&nbsp;Weihao Chen ,&nbsp;Jingshu Chen ,&nbsp;Qiuyue Sun ,&nbsp;Ruiping Zhang","doi":"10.1016/j.ejpb.2025.114714","DOIUrl":"10.1016/j.ejpb.2025.114714","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide with limited therapeutic options due to its tumor immunosuppressive microenvironment (TIME). Herein, we engineered extracellular vehicles (EVs) derived from hepatocellular carcinoma cells to encapsulate rapamycin-loaded nanoparticles (Rapa-EVs) for precision HCC therapy. The experimental results demonstrated that the Rapa-EVs improved water solubility and stability. Rapa-EVs showed a high cellular uptake rate and could effectively target tumor tissues, promote dendritic cell (DC) maturation, and thereby activated CD8 + T cells. They directly inhibited H22 cell proliferation, promoted macrophage M1 polarization. Rapa-EVs also normalized aberrant tumor vasculature to improve drug perfusion and immune cell infiltration, inhibited tumor metastasis. This design synergistically harnesses the natural tumor-targeting properties of EVs to achieve rapamycin-selective delivery, concurrently leveraging their intrinsic immunogenicity to prime antitumor immunity while coordinating rapamycin-mediated TIME remodeling. Through comprehensive in vitro and in vivo evaluations, our study establishes a paradigm for HCC therapy that integrates biomimetic drug delivery with microenvironmental modulation, offering a transformative approach to overcome treatment resistance and improve patient outcomes.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114714"},"PeriodicalIF":4.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimally invasive treatment of fungal keratitis with voriconazole microneedle corneal patch","authors":"Jie Hu ,&nbsp;Di Zhang ,&nbsp;Shuli Chen ,&nbsp;Xin Wang ,&nbsp;Zhiyun Zheng ,&nbsp;Shuangying Gui ,&nbsp;Ning He","doi":"10.1016/j.ejpb.2025.114717","DOIUrl":"10.1016/j.ejpb.2025.114717","url":null,"abstract":"<div><div>Fungal keratitis, a disease caused by fungal infection of the cornea, is an eye disease with a high rate of blindness. Despite voriconazole (VCZ) has a good therapeutic effect in the treatment of fungal infection, the use of VCZ in the eye is limited due to the poor solubility of VCZ and the special physiological structure of the eye. In this study, a soluble microneedle (MN) containing VCZ micelles was designed for the eye to effectively deliver VCZ for the treatment of fungal keratitis. The water-insoluble VCZ was first encapsulated into the micelle prepared by polyethylene glycol-15-hydroxystearate (HS-15), and then mixed with hyaluronic acid (HA) and polyvinylpyrrolidone K30 (PVP K30) to create the microneedle patches loaded with voriconazole micelles (VCZ-MN) using a simple mold molding method. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis showed that VCZ was amorphous dispersed in the MN patch. According to in vitro drug release studies, MN patches can consistently release drugs within 6 h. Following the in vivo application of MN, the retention time in the eye is extended to more than 3 h and has good eye biocompatibility. In addition, MN can reversibly penetrate the corneal epithelium and recover within 24 h. The results of in vitro antibacterial study showed that VCZ-MN had good antibacterial activity. The results of eye tissue distribution showed that maximum concentration (<em>C</em>_max) and area under the concentration–time curve from time zero to infinity (<em>AUC</em>_0-∞) in cornea and aqueous humor in MN group were significantly higher than those in eye drops group. The results indicated that VCZ-MN could significantly increase the concentration of VCZ in eye tissue and eye bioavailability. Therefore, VCZ-MN as a minimally invasive drug delivery device, can be used as a safe and effective way to treat fungal keratitis.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114717"},"PeriodicalIF":4.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of mucoadhesive films with high polaprezinc content for oral mucositis: A study on formulation and near-infrared spectroscopy-based quality control","authors":"Takuya Ito ,&nbsp;Eriko Yamazoe ,&nbsp;Miyui Funato ,&nbsp;Takaaki Ito ,&nbsp;Akio Suzuki ,&nbsp;Kohei Tahara","doi":"10.1016/j.ejpb.2025.114707","DOIUrl":"10.1016/j.ejpb.2025.114707","url":null,"abstract":"<div><div>Polaprezinc (PLZ) has drawn attention to its potential to prevent oral mucositis caused by chemotherapy and radiotherapy. PLZ-containing lozenges have been developed in previous reports; however, for patients with mucositis, taking them may be challenging because of pain. Therefore, this study aimed to develop a mucoadhesive film containing the same amount (18.75 mg) of PLZ as a lozenge as a new dosage form to replace lozenges and evaluate its characteristics. First, various films were created using solvent casting to screen polymers with high PLZ content. Thus, hydroxypropyl cellulose (HPC) was selected; however, film curvature and reduced flexibility necessitated formulation optimization. The optimized films exhibited excellent content uniformity, stability, and mucoadhesive properties, with no significant changes in the drug content after storage. Furthermore, the possibility of using portable near-infrared spectroscopy (Micro NIR™) for the quality control of PLZ films was investigated. Multivariate analysis revealed that the Micro NIR calibration model predicted drug concentrations comparable to those measured by high-performance liquid chromatography. These results suggest that a mucoadhesive film with high PLZ content has been developed and that efficient quality control is possible using Micro NIR™.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114707"},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating structure of endogenous phospholipids on in vivo absorption of octreotide following lung administration","authors":"Lu Qin ,&nbsp;Qiyao Zhai ,&nbsp;Zhixiang Cui ,&nbsp;Hongfang Li ,&nbsp;Jian Guan ,&nbsp;Ziwei Zhang ,&nbsp;Enyu Xu ,&nbsp;Xin Zhang ,&nbsp;Shirui Mao","doi":"10.1016/j.ejpb.2025.114706","DOIUrl":"10.1016/j.ejpb.2025.114706","url":null,"abstract":"<div><div>Phospholipids as endogenous pulmonary components have received extensive attention on promoting the transmembrane absorption of peptides and proteins. However, considering their diversified structure, influence of phospholipid structural characteristics on drug absorption across lung epithelial cells, together with the underlying absorption-promoting mechanisms, remain unclear. Therefore, in this study, taking octreotide as a model drug, phospholipids with different “tail” and “head” structures were adopted in the form of blank liposomes to investigate their structural characteristics on drug absorption utilizing both 3D Transwell cell models and Sprague Dawley rats. It was demonstrated that indeed the absorption-enhancing capacity of phospholipids was their structure-dependent. Among the tail (non-polar) structures, a moderately increased alkyl chain length could facilitate drug absorption across the pulmonary epithelium, with the highest enhancement ratio observed for Dipalmitoyl Phosphatidylcholine (DPPC) containing a palmitoyl group of 16 carbons, and its apparent permeability coefficient (<em>P_app</em>) increased 2.4 times compared to octreotide solution. Among the head (polar) structures, charged functional groups could contribute to better drug permeation, and Dipalmitoyl Phosphatidylserine (DPPS) containing a protonated amino (<img>NH₃⁺) and a deprotonated carboxyl (<img>COO^-) exhibited a 4.6-fold increase in <em>P_app</em> compared to octreotide solution. Mechanism studies disclosed a paracellular pathway-mediated drug transport across lung epithelial cells. In summary, phospholipids can serve as biosafe absorption enhancers for pulmonary drug delivery, with the extent depending on their structure, which could provide a theoretical basis for pulmonary delivery of macromolecules for systemic absorption.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114706"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and characterization of a multifunctional hyaluronic acid-based microneedle system for diabetic wound healing","authors":"Jianmin Chen ,&nbsp;Wenqin Zhang ,&nbsp;Xinyi Zhang ,&nbsp;Yuelian Zhang ,&nbsp;Guozhong Yang ,&nbsp;Dechao Yang ,&nbsp;Yunhua Gao","doi":"10.1016/j.ejpb.2025.114704","DOIUrl":"10.1016/j.ejpb.2025.114704","url":null,"abstract":"<div><div>Diabetes mellitus (DM)-associated wounds, characterized by chronic bacterial infections and elevated glucose levels, present significant challenges to effective healing. To overcome these issues, a novel transdermal drug delivery system was developed, integrating microneedles (MNs) with biofilm-penetrating capability, the wound-healing properties of hyaluronic acid (HA), the antibacterial effects of silver nanoparticles (AgNPs), and the glucose-lowering action of insulin (Ins). Named HAMNs@AgNPs-Ins, this system demonstrated optimal morphological characteristics, robust mechanical strength, and 100 % skin penetration efficiency. It exhibited sustained antibacterial activity <em>in vitro</em>, ensured skin safety, and provided controlled, steady blood glucose reductions, achieving a 72.29 % reduction at 8 h, compared to the sharp decline seen with subcutaneous injection. Additionally, wound healing experiments showed a significant improvement in the healing rate of 89.66 ± 1.34 % in the HAMNs@AgNPs-Ins group, compared to 48.19 ± 9.03 % in the control group. These results underscore the potential of HAMNs@AgNPs-Ins as an effective treatment for DM-associated wounds.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114704"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravitreal CBD-loaded niosomes enhance retinal neuroprotection in ischemic injury","authors":"Carolina Nunes Silva ,&nbsp;Lays Fernanda Nunes Dourado ,&nbsp;Bárbara Leão Agata ,&nbsp;Maísa Angélica Silva Fernandes ,&nbsp;Marina França Dias ,&nbsp;Sílvia Ligorio Fialho","doi":"10.1016/j.ejpb.2025.114705","DOIUrl":"10.1016/j.ejpb.2025.114705","url":null,"abstract":"<div><div>Cannabidiol (CBD) has emerged as a promising treatment for conditions like retinal ischemia, characterized by reduced blood flow to the retina and significant vision loss. Despite its therapeutic potential, CBD’s clinical application could be limited by due to its low bioavailability. This study investigates the efficacy of CBD-loaded niosomes as a neuroprotective formulation for the use in ocular therapies related to retinal ischemia. We investigated the neuroprotective effects of CBD using a nanodispersed system (niosomes) administered via intravitreal injection in rats’ eyes. Niosomes underwent characterization for size, distribution, zeta potential, morphology, and encapsulation efficiency. Safety and neuroprotective activity were assessed by electroretinography (ERG), confocal and transmission microscopy and histology. Niosomes exhibited nanometric size (100–400 nm) and stability, showing good tolerance in animals. ERG results demonstrated higher b-wave amplitudes in animals pre-treated with niosomes + CBD compared to the control group following ischemic injury induced by a sudden increase in IOP. Histological and confocal microscopy analyses of retinas from the niosomes + CBD group showed preserved structure compared to the ischemic control group, suggesting significant retinal protection by intravitreally injected niosomes + CBD before ischemia. CBD-loaded niosomes effectively preserved retinal function, highlighting the neuroprotective potential of CBD against retinal ischemia. This formulation presents a promising and innovative treatment for ischemic retinal diseases.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114705"},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability of Jurkat cells during short-term liquid storage analyzed by flow imaging microscopy","authors":"Alexandra Roesch ,&nbsp;Cornelia Hiemenz ,&nbsp;Teresa Findley ,&nbsp;Ilya Goldberg ,&nbsp;Roland Windisch ,&nbsp;Christian Wichmann ,&nbsp;Gideon Kersten ,&nbsp;Tim Menzen","doi":"10.1016/j.ejpb.2025.114703","DOIUrl":"10.1016/j.ejpb.2025.114703","url":null,"abstract":"<div><div>The viability of cell-based medicinal products (CBMPs) is a critical quality attribute and must be assessed throughout the product lifecycle to contribute to a safe and potent drug product. In this study, we investigated the impact of short-term liquid storage conditions, encountered during manufacturing of CBMPs, such as holding times outside cell culture conditions and medium composition, on cell viability.</div><div>As a model for T cells Jurkat cells were used and stored in different storage media for up to 24 h outside a freezer and outside of cell culture conditions. The effect of storage in different storage media, i.e., cell culture medium or phosphate buffered saline (PBS), dimethyl sulfoxide (DMSO) at different storage temperatures as well as the impact of pH on the cell viability was assessed. The viability of the cells was assessed by (i) flow cytometry with an Annexin V and CalceinAM staining or (ii) machine learning tools, leveraging the morphological information of flow imaging microscopy images. Cell images obtained by flow imaging microscopy were analyzed with both the ParticleSentry^AI imaging software and a convolutional neural network (CNN) for fast and semi-automated viability assessment.</div><div>Throughout storage conditions similar to those during processing of CBMPs, a decrease in cell viability was observed over time for all conditions based on Annexin V and CalceinAM staining. Additionally, we observed a damaging effect of DMSO over time, whereas this effect was more pronounced at room temperature compared to refrigerated temperatures. The ParticleSentry^AI software was useful to detect qualitative differences in the cell viability as a shift towards non-viable cells could be observed throughout storage based on flow imaging microscopy images without prior sample preparation. Viability determination based on the CNN underestimated cell viability when compared to the flow cytometry assays, however the same trends were determined.</div><div>In summary, non-frozen storage of CBMPs should be kept to a minimum. However, standing times throughout the manufacturing of CBMPs as well as during in-use cannot be completely avoided and therefore, the optimal storage conditions have to be carefully evaluated. Additionally, further analytical development is needed to implement machine learning tools suitable for reliable viability quantification without additional sample preparation such as staining.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"211 ","pages":"Article 114703"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaginal formulation development: A strategy based on aptamer-guided liposome for human papillomavirus-induced lesions","authors":"Jéssica Lopes-Nunes ,&nbsp;Melanie Lopes ,&nbsp;Beatriz Rosado ,&nbsp;Izamara Gomes Maocha ,&nbsp;Joana Rolo ,&nbsp;Carlos Gaspar ,&nbsp;Bruno Pires ,&nbsp;Tiago Rosado ,&nbsp;Eugénia Gallardo ,&nbsp;Ana Palmeira-de-Oliveira ,&nbsp;José Martinez-de-Oliveira ,&nbsp;Catarina Ferreira ,&nbsp;Maria Paula Cabral Campello ,&nbsp;António Paulo ,&nbsp;Beatriz Medeiros-Fonseca ,&nbsp;Luís Félix ,&nbsp;Carlos Venâncio ,&nbsp;Maria de Lurdes Pinto ,&nbsp;Paula A. Oliveira ,&nbsp;Rita Palmeira-de-Oliveira ,&nbsp;Carla Cruz","doi":"10.1016/j.ejpb.2025.114693","DOIUrl":"10.1016/j.ejpb.2025.114693","url":null,"abstract":"<div><div>Human Papillomavirus (HPV) is the main cause of cervical cancer, and formulations have been widely used to treat vaginal lesions caused by HPV.</div><div>Herein, liposomes with acridine orange derivative C₈ were produced and functionalized with AT11 aptamer. Subsequently, they were incorporated into a formulation, prepared based on the universal placebo formulation, which included <em>Thymus vulgaris</em> (TEO) or <em>Origanum vulgare</em> (OEO) essential oils. The formulation was technologically characterized and permeation of C₈ into vaginal tissue was determined. To assess its biological effect, cell viability and internalization tests were carried out using the MTT assay and confocal microscopy, respectively, and antimicrobial susceptibility was also assessed. The prepared formulations were able to internalize cells and reduce cell viability, especially in cancer cell lines. Additionally, formulations showed promising antibacterial and antifungal effects. The effect of the formulation containing TEO and the C₈ AT11 liposomes was also tested <em>in vivo</em> in HPV16 transgenic and wild type mice. Briefly, the formulation proved to be safe for animals and presented some therapeutic potential, namely through the reduction of ear epithelial cells’ proliferation. Overall, results suggest that essential oils can increase the anticancer potential of liposomes with associated C₈ and AT11 promotes their selectivity towards cancer cells.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"210 ","pages":"Article 114693"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}