Drug Delivery and Translational Research最新文献

Blended ƙ-carrageenan and xanthan gum hydrogel containing ketoprofen-loaded nanoemulsions: Design, characterization, and evaluation in an animal model of rheumatoid arthritis. 混合ƙ-carrageenan和黄原胶水凝胶含有酮洛芬负载纳米乳液：设计，表征和类风湿关节炎动物模型的评估。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-16 DOI: 10.1007/s13346-024-01786-5

Marcel Henrique Marcondes Sari, Verônica Ferrari Cervi, Vanessa Neuenschwander Custódio, Vinicius Costa Prado, Ketlyn Pereira da Motta, Cristiane Luchese, Ethel Antunes Wilhelm, Luana Mota Ferreira, Letícia Cruz

{"title":"Blended ƙ-carrageenan and xanthan gum hydrogel containing ketoprofen-loaded nanoemulsions: Design, characterization, and evaluation in an animal model of rheumatoid arthritis.","authors":"Marcel Henrique Marcondes Sari, Verônica Ferrari Cervi, Vanessa Neuenschwander Custódio, Vinicius Costa Prado, Ketlyn Pereira da Motta, Cristiane Luchese, Ethel Antunes Wilhelm, Luana Mota Ferreira, Letícia Cruz","doi":"10.1007/s13346-024-01786-5","DOIUrl":"10.1007/s13346-024-01786-5","url":null,"abstract":"This study reports the preparation of hydrogels (HG) made with xanthan gum (XG) and ƙ-carrageenan (KC) polysaccharides containing ketoprofen (KET)-loaded nanoemulsions (NK) and their evaluation in a rheumatoid arthritis (RA) model. The nano-based HGs exhibited nanometric-sized droplets (~ 100 nm), an acidic pH (5.10-6.83), drug content above 85%, a suitable spreadability factor, and pseudoplastic flow behavior. The most promising blend (HGCX 2:1) demonstrated sustained KET release, reaching 81.44 ± 6.11% after 5 h, and superior drug concentration in the skin layers (237.91 ± 41.0 µg/g). The formulation was selected due to its enhanced bioadhesiveness, with the HG-NK formulation showing the highest bioadhesion force and occlusion factor. RA was induced by complete Freund's adjuvant (CFA) intraplantar injection into the left hind paw of male and female Swiss mice. Treatments with HGs were applied to the animals' dorsal region for 7 days. Notably, HG-NK demonstrated remarkable efficacy, reversing mechanical sensitivity in male mice and significantly reducing thermal sensitivity in both genders. Moreover, HG-NK provided a significant reduction in paw edema (52-fold in males, 27-fold in females) and inflammatory markers, such as myeloperoxidase activity (32-fold in males, 14-fold in females) and lipid peroxidation (2.5-fold in males, twofold in females). The formulation also promoted greater permeation of KET across the skin. These findings underscore the significant reduction in inflammatory markers by the HG-NK formulation, highlighting its potent anti-inflammatory effects and potential as a promising therapeutic strategy for managing RA.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2878-2903"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001971","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}

引用次数: 0

Nano-delivery of a novel inhibitor of ERCC1-XPF for targeted sensitization of colorectal cancer to platinum-based chemotherapeutics. 一种新型ERCC1-XPF抑制剂的纳米递送用于结直肠癌对铂基化疗药物的靶向致敏。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-29 DOI: 10.1007/s13346-024-01782-9

Parnian Mehinrad, Ahmed Abdelfattah, Sams M A Sadat, Tanin Shafaati, Ahmed H Elmenoufy, David Jay, Frederick West, Michael Weinfeld, Afsaneh Lavasanifar

{"title":"Nano-delivery of a novel inhibitor of ERCC1-XPF for targeted sensitization of colorectal cancer to platinum-based chemotherapeutics.","authors":"Parnian Mehinrad, Ahmed Abdelfattah, Sams M A Sadat, Tanin Shafaati, Ahmed H Elmenoufy, David Jay, Frederick West, Michael Weinfeld, Afsaneh Lavasanifar","doi":"10.1007/s13346-024-01782-9","DOIUrl":"10.1007/s13346-024-01782-9","url":null,"abstract":"In this study, a novel inhibitor of ERCC1/XPF heterodimerization, A4, was used as an inhibitor of repair for DNA damage by platinum-based chemotherapeutics. Nano-formulations of A4 were developed, using self-assembly of the following block copolymers: methoxy-poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-b-PBCL), methoxy-poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL), or methoxy-poly(ethylene oxide)-block-poly (D, L, lactide) (PEO-b-PDLA 50-50). The nano-formulations were characterized for their average diameter, polydispersity, morphology, A4 encapsulation and in vitro release. The activity of A4 and its nano-formulation on the inhibition of ERCC1/XPF dimerization was investigated. The cytotoxicity of carboplatin and oxaliplatin in colorectal cancer (CRC) cell lines, without or with pre-treatment with A4 or its nanoparticle formulation was assessed by conducting colony forming as well as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Among the three nano-formulations of A4 under study, optimum properties were achieved with PEO-b-PBCL nanocarriers, showing an encapsulation efficiency of 83.1 ± 5.83%, loading content of 11.5 ± 0.37 w/w %, < 50% drug release within 24 hs, and an average diameter of < 150 nm. The chemo sensitizing effect of A4 and its nano-encapsulated counterparts were more noticeable when A4 was combined with carboplatin versus oxaliplatin. The results of cytotoxicity studies in HCT116 XPF-/- cells confirmed the specificity of A4 through an XPF-dependent mechanism in the sensitization of these cells to carboplatin at concentrations below 0.5 μM. The result of the study shows great potential for A4 and its PEO-b-PBCL nano-formulation in sensitization of CRC to platinum-based chemotherapeutics.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2833-2847"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058200","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}

引用次数: 0

Simvastatin is delivered to the brain by high-strength intranasal cationic SMEDDS and nanoemulsions. 辛伐他汀通过高强度的鼻内阳离子SMEDDS和纳米乳液输送到大脑。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-02 DOI: 10.1007/s13346-024-01769-6

Francisco Gama, Sara Meirinho, Patrícia C Pires, Johann Tinoco, Maria Carolina Martins Gaspar, Graça Baltazar, Gilberto Alves, Adriana O Santos

{"title":"Simvastatin is delivered to the brain by high-strength intranasal cationic SMEDDS and nanoemulsions.","authors":"Francisco Gama, Sara Meirinho, Patrícia C Pires, Johann Tinoco, Maria Carolina Martins Gaspar, Graça Baltazar, Gilberto Alves, Adriana O Santos","doi":"10.1007/s13346-024-01769-6","DOIUrl":"10.1007/s13346-024-01769-6","url":null,"abstract":"The repurposing of statins as neuroprotective agents and/or anti-brain tumor drugs is limited by challenges in brain bioavailability and systemic off-target effects. Therefore, improved and targeted delivery of statins to the brain is necessary. This study aimed to develop a high-strength liquid formulation of the poorly soluble prodrug simvastatin for intranasal administration, as a strategy to achieve high brain concentrations of the prodrug and/or its active form, tenivastatin. Cationic simvastatin nanoemulsions (c-NE) and self-microemulsifying drug delivery systems (c-SMEDDS) were screened for composition, extensively characterized, and the viscosity of the nanoemulsion was further optimized. The optimized c-NE and c-SMEDDS formulations achieved high drug strengths, approximately 5.5% and 9% (w/w), respectively. They formed highly homogeneous aqueous dispersions (polydispersity index < 0.1) with small droplet sizes (< 120 nm and ~ 25 nm, respectively) and remained stable for at least four months under refrigeration. Neither the c-NE nor the c-SMEDDS induced hemolysis up to concentrations of 40 µg/mL and 450 µg/mL of simvastatin, respectively. The zero-shear viscosity of the c-NE was increased to 186 mPa·s by incorporating 0.25% (w/w) polyvinylpyrrolidone, which approached the viscosity of the c-SMEDDS (~ 126 mPa·s). Following intranasal administration of the optimized formulations to Wistar rats at a dose of 10 mg/kg, simvastatin levels in the brain reached 50 to 150 ng/g between 15 and 60 min post-administration. These findings indicate that the developed c-NE and c-SMEDDS formulations hold promise for simvastatin intranasal delivery and brain targeting, potentially paving the way for the realization of simvastatin's neuroprotective potential.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2749-2764"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920874","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}

引用次数: 0

Enhancement of cannabidiol oral bioavailability through the development of nanostructured lipid carriers: In vitro and in vivo evaluation studies. 通过开发纳米结构脂质载体提高大麻二酚口服生物利用度：体外和体内评估研究。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2024-12-30 DOI: 10.1007/s13346-024-01766-9

Iman E Taha, Mahmoud A ElSohly, Mohamed M Radwan, Rasha M Elkanayati, Amira Wanas, Poorva H Joshi, Eman A Ashour

{"title":"Enhancement of cannabidiol oral bioavailability through the development of nanostructured lipid carriers: In vitro and in vivo evaluation studies.","authors":"Iman E Taha, Mahmoud A ElSohly, Mohamed M Radwan, Rasha M Elkanayati, Amira Wanas, Poorva H Joshi, Eman A Ashour","doi":"10.1007/s13346-024-01766-9","DOIUrl":"10.1007/s13346-024-01766-9","url":null,"abstract":"Cannabidiol (CBD) is a natural product isolated from the Cannabis sativa plant that was approved by the United States Food and Drug Administration (US FDA) for the treatment of resistant epilepsy. Despite its therapeutic potential, CBD's clinical application is limited by its poor aqueous solubility and low oral bioavailability. The primary aim of this research was to enhance the aqueous solubility and oral bioavailability of CBD by developing nanostructured lipid carriers (NLCs) using conventional hot homogenization method (CHH). In the current study, nine CBD NLC formulations were developed through CHH, of which, NLC5 emerged as the most promising formulation, exhibiting high CBD entrapment efficiency (99.23%), particle size of 207 nm, a polydispersity index of 0.19, and a zeta potential of -26 mV. Additionally, drug release testing for NLC5 showed a high CBD release rate of more than 90% within 15 min, indicating an enhancement of CBD dissolving rate compared to pure CBD. The in vivo pharmacokinetic study of NLC5 formulation showed 27% CBD oral bioavailability. Furthermore, Stability studies conducted at 4 °C and 25 °C on this formulation over three months, revealed consistent parameters, underscoring the robustness of the formulation. In conclusion, the successful formulation of CBD-loaded NLCs resulted in improved CBD release rate, enhanced oral bioavailability of CBD, and maintained stability, making it a promising approach for the effective delivery of CBD.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2722-2732"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908864","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}

引用次数: 0

Optimizing hydrophilic drug incorporation into SEDDS using dry reverse micelles: a comparative study of preparation methods. 利用干燥反胶束优化亲水药物掺入SEDDS：制备方法的比较研究。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-16 DOI: 10.1007/s13346-024-01787-4

Sera Lindner, Fabrizio Ricci, Matthias Sandmeier, René Holm, Cecilia Bohns Michalowski, Nathaniel Washburn, Dajun Sun, Giustino Di Pretoro, Andreas Bernkop-Schnürch

{"title":"Optimizing hydrophilic drug incorporation into SEDDS using dry reverse micelles: a comparative study of preparation methods.","authors":"Sera Lindner, Fabrizio Ricci, Matthias Sandmeier, René Holm, Cecilia Bohns Michalowski, Nathaniel Washburn, Dajun Sun, Giustino Di Pretoro, Andreas Bernkop-Schnürch","doi":"10.1007/s13346-024-01787-4","DOIUrl":"10.1007/s13346-024-01787-4","url":null,"abstract":"Aim: It was the aim of this study to compare two different dry reverse micelle (RM) preparation methods for the incorporation of hydrophilic drugs into oral self-emulsifying drug delivery systems (SEDDS).Methods: Cationic ethacridine lactate, anionic fluorescein sodium salt and the antibiotic peptide bacitracin were solubilized in RM containing sodium docusate, soy phosphatidylcholine and sorbitan monooleate in highly lipophilic oils such as squalane. In the dry addition (DA) method, drugs were directly added to empty RM in their powder form. In the organic solvent-aided (OS) method, drugs were pre-dissolved in ethanol or 2-propanol, which were then evaporated to form loaded dry RM.Results: RM with sorbitan monooleate prepared via the DA method yielded up to 2.7-fold higher solubility only for bacitracin compared to the OS method. In contrast, OS-RM with sodium docusate and soy phosphatidylcholine exhibited significantly higher drug solubilities, achieving up to 109-fold, 44-fold and 97-fold increase for ethacridine, fluorescein and bacitracin, respectively. For all model drugs, the logDlipophilic phase/water was highest for RM comprising sorbitan monooleate, with a slight increase for OS-RM. This was consistent with the release profiles from SEDDS, showing an enhanced retention when loaded with OS-RM. While DA-RM showed no significant difference in cellular uptake, it was 1.6-fold higher in OS-RM loaded squalane-based SEDDS.Conclusion: The DA method is an easier approach for incorporating hydrophilic drugs into dry RM. However, the OS method presents a more promising alternative as it significantly enhanced the solubility and retention of these drugs in highly lipophilic formulations.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2904-2923"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001983","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}

引用次数: 0

Revolutionizing Parkinson's treatment: Harnessing the potential of intranasal nanoemulsions for targeted therapy. 革新帕金森病治疗：利用鼻内纳米乳剂靶向治疗的潜力。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-08 DOI: 10.1007/s13346-024-01770-z

Gulshan Sharma, Karan Wadhwa, Shobhit Kumar, Govind Singh, Rakesh Pahwa

{"title":"Revolutionizing Parkinson's treatment: Harnessing the potential of intranasal nanoemulsions for targeted therapy.","authors":"Gulshan Sharma, Karan Wadhwa, Shobhit Kumar, Govind Singh, Rakesh Pahwa","doi":"10.1007/s13346-024-01770-z","DOIUrl":"10.1007/s13346-024-01770-z","url":null,"abstract":"Parkinson's disease (PD) is the most prominent and highly prevalent chronic neuro-degenerative disease generally recognized by classical motor symptoms which are linked with genetic mutation, Lewy bodies, and subsequently selective loss of nigrostriatal dopaminergic neurons. The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier protect the central nervous system against toxins and are the most significant barriers to effective brain drug delivery in managing Parkinsonism. In recent years, intranasal delivery has attracted remarkable attention for brain targeting as the drug can be administered to the brain directly from the nose employing the trigeminal and olfactory pathways. For brain targeting through nasal delivery, several advanced and promising formulation techniques have been investigated globally. Nanoemulsions are regarded as an innovative carrier approach for PD, where these provide targeted administration and enhanced bioavailability of neurotherapeutics. This manuscript provides deeper insight into the pathophysiology of PD, various drug delivery strategies to overcome BBB, and the potential role of nanoemulsions via the intranasal route. Various research findings on the intranasal administration of nanoemulsions and their pivotal applications in the treatment of PD have also been embarked. The potential role of phytoconstituents and surface-modified nanoemulsions for the effective treatment of PD has also been reflected along with current challenges and future perspectives in this avenue.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2589-2607"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946529","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}

引用次数: 0

Quality-by-design principles applied to the development and optimisation of lidocaine-loaded dissolving microneedle arrays - a proof-of-concept. 设计质量原则应用于利多卡因溶解微针阵列的开发和优化-概念验证。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-03 DOI: 10.1007/s13346-024-01758-9

Pei Gie Yong, Ana-Manuela Segorean, Ana Sara Cordeiro

{"title":"Quality-by-design principles applied to the development and optimisation of lidocaine-loaded dissolving microneedle arrays - a proof-of-concept.","authors":"Pei Gie Yong, Ana-Manuela Segorean, Ana Sara Cordeiro","doi":"10.1007/s13346-024-01758-9","DOIUrl":"10.1007/s13346-024-01758-9","url":null,"abstract":"The use of dissolving microneedle arrays (dMNA) for intradermal and transdermal drug delivery has been a growing trend in the field for the past decades. However, a lack of specific regulatory standards still hinders their clinical development and translation to market. It is also well-known that dMNA composition significantly impacts their performance, with each new formulation potentially presenting a challenge for developers, manufacturers and regulatory agencies. A systematic approach such as quality-by-design (QbD), which embeds quality from the very beginning of the product development process, allows the design and optimisation of a drug-loaded dMNA formulation with promising features. In this work, we defined the Quality Target Product Profile (QTPP) for lidocaine-loaded dMNA and optimised their composition through a sequential design of experiments (DoE) approach. The first step (DoE_1) confirmed the influence of all formulation components (PVP, PVA and sucrose) in the properties of the arrays and pre-optimised their settings for DoE_2. The array characterisation focused on previously defined critical quality attributes (drug content, dissolution time, mechanical strength, skin insertion and physical attributes). At its maximum desirability (85.15%), the optimised design space obtained in DoE_2 is predicted to produce Li-dMNA with high mechanical strength (< 10% needle height reduction), skin insertion (> 90% needle height) and Li-HCl loading (~ 5 mg), good physical attributes and dissolving in a maximum of 60 min. The flexible design space obtained allows for the production of dMNA that consistently meet the QTPP, reducing batch failure and end-product testing, which are common in the more rigid GMP approach. Overall, applying QbD principles to formulation development shows promise to increase product quality and facilitate translation of dMNA into the clinic.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2643-2662"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920928","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}

引用次数: 0

Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method. lintt1 -肽偶联对纳米沉淀法制备聚乙二醇嵌段-（ε-己内酯）纳米颗粒性能的影响

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-03 DOI: 10.1007/s13346-024-01768-7

Voitto Känkänen, Sami-Pekka Hirvonen, Tambet Teesalu, Jouni Hirvonen, Vimalkumar Balasubramanian, Hélder A Santos

{"title":"Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.","authors":"Voitto Känkänen, Sami-Pekka Hirvonen, Tambet Teesalu, Jouni Hirvonen, Vimalkumar Balasubramanian, Hélder A Santos","doi":"10.1007/s13346-024-01768-7","DOIUrl":"10.1007/s13346-024-01768-7","url":null,"abstract":"Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) \"post-conjugation\" onto pre-formed nanoparticles, and (2) \"pre-conjugation\", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements. Characterization of NPs with respect to particle size, zeta potential, morphology and peptide content was performed, and their ability to bind to the target protein p32 was tested using a cell-free assay. Importantly, both methods resulted in NPs that were able to bind their target when methyl-terminated PCL-PEG used as the diluent polymer, but not when acid-terminated polymer was used. Moreover, peptide conjugation induced a morphological transformation from spheres to vesicles regardless of the conjugation method used. However, smaller and more homogeneous NPs were obtained by the pre-conjugation method.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2733-2748"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926666","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}

引用次数: 0

Cutting-edge insights into liver fibrosis: advanced therapeutic strategies and future perspectives using engineered mesenchymal stem cell-derived exosomes. 肝纤维化的前沿研究：利用工程化间充质干细胞衍生外泌体的先进治疗策略和未来前景。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-24 DOI: 10.1007/s13346-024-01784-7

Manar A Didamoony, Ayman A Soubh, Lamiaa A Ahmed

{"title":"Cutting-edge insights into liver fibrosis: advanced therapeutic strategies and future perspectives using engineered mesenchymal stem cell-derived exosomes.","authors":"Manar A Didamoony, Ayman A Soubh, Lamiaa A Ahmed","doi":"10.1007/s13346-024-01784-7","DOIUrl":"10.1007/s13346-024-01784-7","url":null,"abstract":"Liver fibrosis is still a serious health concern worldwide, and there is increasing interest in mesenchymal stem cells (MSCs) with tremendous potential for treating this disease because of their regenerative and paracrine effects. Recently, many researches have focused on using the released exosomes (EXOs) from stem cells to treat liver fibrosis rather than using parent stem cells themselves. MSC-derived EXOs (MSC-EXOs) have demonstrated favourable outcomes similar to cell treatment in terms of regenerative, immunomodulatory, anti-apoptotic, anti-oxidant, anti-necroptotic, anti-inflammatory and anti-fibrotic actions in several models of liver fibrosis. EXOs are superior to their parent cells in several terms, including lower immunogenicity and risk of tumour formation. However, maintaining the stability and efficacy of EXOs after in vivo transplantation remains a major challenge in their clinical applicability. Therefore, several strategies have been applied in EXOs engineering, such as parental cell modification or modifying EXOs directly to achieve optimum performance of EXOs in treating liver fibrosis. Herein, we discuss the underlying mechanisms of liver fibrosis with an overview of the available therapies, among them EXOs. We also summarise the recent developments in improving the effectiveness of EXOs with the advantages and limitations of these approaches in terms of the upcoming clinical applications.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2608-2623"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032625","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}

引用次数: 0

Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields. 巨噬细胞与药物相关和超顺磁性纳米颗粒共载，通过交变磁场触发药物释放。

IF 5.7 3区医学

Drug Delivery and Translational Research Pub Date : 2025-08-01 Epub Date: 2025-01-13 DOI: 10.1007/s13346-024-01774-9

Omkar Desai, Sandhya Kumar, Mario Köster, Sami Ullah, Sushobhan Sarker, Valentin Hagemann, Mosaieb Habib, Nicole Klaassen, Silke Notter, Claus Feldmann, Nina Ehlert, Hansjörg Hauser, Dagmar Wirth

{"title":"Macrophages co-loaded with drug-associated and superparamagnetic nanoparticles for triggered drug release by alternating magnetic fields.","authors":"Omkar Desai, Sandhya Kumar, Mario Köster, Sami Ullah, Sushobhan Sarker, Valentin Hagemann, Mosaieb Habib, Nicole Klaassen, Silke Notter, Claus Feldmann, Nina Ehlert, Hansjörg Hauser, Dagmar Wirth","doi":"10.1007/s13346-024-01774-9","DOIUrl":"10.1007/s13346-024-01774-9","url":null,"abstract":"Two features of macrophages make them attractive for targeted transport of drugs: they efficiently take up a broad spectrum of nanoparticles (NPs) and, by sensing cytokine gradients, they are attracted to the sites of infection and inflammation. To expand the potential of macrophages as drug carriers, we investigated whether macrophages could be simultaneously coloaded with different types of nanoparticles, thus equipping individual cells with different functionalities. We used superparamagnetic iron oxide NPs (SPIONs), which produce apoptosis-inducing hyperthermia when exposed to an alternating magnetic field (AMF), and co-loaded them on macrophages together with drug-containing NPs (inorganic-organic nanoparticles (IOH-NPs) or mesoporous silica NPs (MSNs)). We show that individual macrophages can take up both SPIONs and drug-loaded NPs efficiently, thereby generating drug-loaded cells susceptible to AMF-induced cell death. Macrophages co-loaded with SPIONs and drug-containing IOH-NPs spontaneously released the drugs at similar rates irrespective of the application of an AMF. Notably, while the spontaneous drug release from macrophages co-loaded with SPIONs and drug-associated MSNs was low, AMF exposure accelerated the drug release. Thus, AMF exposure of SPION/drug-MSN coloaded macrophages provides a simple strategy for trigger-controlled drug release since it does not require any chemical modification of NPs or drugs. Thus, we assume that the coloading of different types of NPs will expand the potential of macrophages for drug delivery.","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2779-2793"},"PeriodicalIF":5.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970029","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}

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