European Journal of Pharmaceutics and Biopharmaceutics最新文献

{"title":"Pharmaceutical approaches for enhancing solubility and oral bioavailability of poorly soluble drugs","authors":"Isaïe Nyamba ,&nbsp;Charles B Sombié ,&nbsp;Moussa Yabré ,&nbsp;Hermine Zimé-Diawara ,&nbsp;Josias Yaméogo ,&nbsp;Salfo Ouédraogo ,&nbsp;Anna Lechanteur ,&nbsp;Rasmané Semdé ,&nbsp;Brigitte Evrard","doi":"10.1016/j.ejpb.2024.114513","DOIUrl":"10.1016/j.ejpb.2024.114513","url":null,"abstract":"<div><div>High solubility in water and physiological fluids is an indispensable requirement for the pharmacological efficacy of an active pharmaceutical ingredient. Indeed, it is well established that pharmaceutical substances exhibiting limited solubility in water are inclined towards diminished and inconsistent absorption following oral administration, consequently resulting in variability in therapeutic outcomes. The current advancements in combinatorial chemistry and pharmaceutical design have facilitated the creation of drug candidates characterized by increased lipophilicity, elevated molecular size, and reduced aqueous solubility. Undoubtedly, the issue of poorly water-soluble medications has been progressively escalating over recent years. Indeed, 40% of the top 200 oral medications marketed in the United States, 33% of drugs listed in the US pharmacopoeia, 75% of compounds under development and 90% of new chemical entities are insufficiently water-soluble compounds. In order to address this obstacle, formulation scientists employ a variety of approaches, encompassing both physical and chemical methods such as prodrug synthesis, salt formation, solid dispersions formation, hydrotropic substances utilization, solubilizing agents incorporation, cosolvent addition, polymorphism exploration, cocrystal creation, cyclodextrins complexation, lipid formulations, particle size reduction and nanoformulation techniques. Despite the utilization of these diverse approaches, the primary reason for the failure in new drug development persists as the poor aqueous solubility of pharmaceutical compounds. This paper, therefore, delves into the foundational principles that underpin the implementation of various formulation strategies, along with a discussion on the respective advantages and drawbacks associated with each approach. Additionally, a discourse is provided regarding methodological frameworks for making informed decisions on selecting an appropriate formulation strategy to effectively tackle the key challenges posed during the development of a poorly water-soluble drug candidate.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114513"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307390","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":"Intratracheal delivery of macrophage targeted Celastrol-loaded PLGA nanoparticles for enhanced anti-inflammatory efficacy in acute lung injury mice","authors":"Yinlian Yao ,&nbsp;Shilong Fan ,&nbsp;Yinqiang Fan ,&nbsp;Xin Shen ,&nbsp;Xingxing Chai ,&nbsp;Jiang Pi ,&nbsp;Xueqin Huang ,&nbsp;Yiming Shao ,&nbsp;Zhikun Zhou ,&nbsp;Yue Zhao ,&nbsp;Hua Jin","doi":"10.1016/j.ejpb.2024.114511","DOIUrl":"10.1016/j.ejpb.2024.114511","url":null,"abstract":"<div><div>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. <em>In vitro</em> data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. <em>In vivo</em> experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114511"},"PeriodicalIF":4.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282518","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":"Characterization of naproxen salts with amino acid esters and their application in topical skin preparations","authors":"Ewelina Kopciuch ,&nbsp;Ewa Janus ,&nbsp;Paula Ossowicz-Rupniewska ,&nbsp;Anna Nowak ,&nbsp;Wiktoria Duchnik ,&nbsp;Łukasz Kucharski ,&nbsp;Urszula Adamiak-Giera ,&nbsp;Zofia Lendzion-Bieluń","doi":"10.1016/j.ejpb.2024.114505","DOIUrl":"10.1016/j.ejpb.2024.114505","url":null,"abstract":"<div><div>In the study, the modification of naproxen (NAP) with esters of four amino acids (AAs): glycine (GlyOiPr), L-proline (ProOiPr), L-leucine (LeuOiPr), and L-serine (SerOiPr) <em>iso</em>propyl ester was performed to improve water solubility and enhance the permeation of the drug through the skin in comparison to the parent NAP. The NAP derivatives were prepared using the equimolar ratio of the components. In-depth NMR and FTIR analysis revealed that the salts formed with the proton transfer from the carboxylic group of NAP to the amine group of the appropriate AA ester. The NAP salts exhibited improved solubility in water and PBS solution (pH 7.4) when compared to parent NAP. The values of the partition coefficient (log P_O/W) for prepared salts were lower than for NAP, however, the salts maintained hydrophobic character determined by the positive values of log P. The <em>In vitro</em> permeation through the pig skin performed in Franz diffusion cells showed that all NAP salts exhibited a higher cumulative mass of permeated NAP (Q_24h) than the parent acid. The highest permeation value was noted for [ProOiPr][NAP], with a pseudo-steady state flux (J_ss) 32.5 µg NAP cm⁻²h⁻¹, and Q_24h = 246.4 µg NAP cm⁻², it was 2.5 % of the applied dose. Moreover, topical preparations with [ProOiPr][NAP] and NAP were prepared based on two vehicles − Celugel® and Pentravan®- approved in pharmacy recipes. The permeation experiments through the Strat-M® showed, that both the J_ss and Q_24h of permeated drug from preparations containing [ProOiPr][NAP], were statistically several times greater than from the respective preparations with the unmodified acid. Additionally, preparations with [ProOiPr][NAP] provided significantly improved permeation of NAP than two commercial preparations, one of which contained naproxen as the acid and the other – as the sodium salt.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114505"},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282513","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":"Design and development of Fujicalin-based axitinib liquisolid compacts for improved dissolution and bioavailability to treat renal cell carcinoma","authors":"Priyanka S. Yadav ,&nbsp;Ashok A. Hajare ,&nbsp;Kiran S. Patil","doi":"10.1016/j.ejpb.2024.114506","DOIUrl":"10.1016/j.ejpb.2024.114506","url":null,"abstract":"<div><div>Poor dissolution of axitinib (AXT) limits its effectiveness through the oral route. The present study investigated, prospective of liquisolid (LS) technology to improve dissolution rate and oral bioavailability of AXT to treat renal cell carcinoma. LS compacts were fabricated with PEG 200, Fujicalin SG, and Aerosil 200 as solvent, carrier, and coat material, respectively. The behavior of LS-systems during tabletting was investigated using Kawakita, Heckel, and Leuenberger analysis. LS compacts were examined for <em>P</em>-XRD, DSC, SEM, and <em>in vitro</em> drug dissolution. For optimization, a 3² full factorial design was utilized. Cell line A498 was utilized for <em>in vitro</em> cytotoxicity study. A bioavailability study was performed using rabbits. DSC and <em>P</em>-XRD analysis confirmed the transition of crystalline AXT to its partial amorphization and molecular dispersion. Consequently, LS6 demonstrated a significantly rapid drug dissolution (Q₂₀; &gt;99 %) than the directly compressed tablets (18.05 %). Additionally, 2.03-fold increase in oral bioavailability, and inhibited dose-dependent cell growth with 1.75-fold increased apoptosis rate. Overall, an LS6 compact consisting of 15 % AXT concentration in PEG 200 and a 20 w/w ratio of Fujicalin SG: Aerosil 200 exhibited improved formulation properties, enhanced dissolution rate, and bioavailability. Thus developed potential product may contribute low-cost production with patient-improved survival expectations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114506"},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282514","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":"Low pinocytic brain endothelial cells primarily utilize membrane fusion to internalize extracellular vesicles","authors":"Jhanvi R. Jhaveri ,&nbsp;Purva Khare ,&nbsp;Paromita Paul Pinky ,&nbsp;Yashika S. Kamte ,&nbsp;Manisha N. Chandwani ,&nbsp;Jadranka Milosevic ,&nbsp;Nevil Abraham ,&nbsp;Ming Sun ,&nbsp;Donna B. Stolz ,&nbsp;Kandarp M. Dave ,&nbsp;Si-yang Zheng ,&nbsp;Lauren O’Donnell ,&nbsp;Devika S Manickam","doi":"10.1016/j.ejpb.2024.114500","DOIUrl":"10.1016/j.ejpb.2024.114500","url":null,"abstract":"<div><div>Extracellular vesicles (<strong>EVs</strong>) are an emerging class of drug carriers and are primarily reported to be internalized into recipient cells via a combination of endocytic routes such as clathrin-mediated, caveolae-mediated and macropinocytosis pathways. In this work, (1) we investigated potential effects of homotypic <em>vs</em>. heterotypic interactions by studying the cellular uptake of homologous EVs (EV donor cells and recipient cells of the same type) <em>vs</em>. heterologous EVs (EV donor cells and recipient cells of different types) and (2) determined the route of EV internalization into low pinocytic/hard-to-deliver cell models such as brain endothelial cells (<strong>BECs</strong>). Homotypic interactions led to a greater extent of uptake into the recipient BECs compared to heterotypic interactions. However, we did <em>not</em> see a complete reduction in EV uptake into recipient BECs when endocytic pathways were blocked using pharmacological inhibitors and our findings from a R18-based fusion assay suggest that EVs primarily use membrane fusion to enter low-pinocytic recipient BECs instead of relying on endocytosis. <em>Lipophilic PKH67 dye-labeled EVs</em> but not intravesicular esterase-activated calcein ester-labeled EVs severely reduced particle uptake into BECs while phagocytic macrophages internalized EVs labeled with both dyes to comparable extents. Our results also highlight the importance of carefully choosing labeling dye chemistry to study EV uptake, especially in the case of low pinocytic cells such as BECs.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114500"},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282533","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":"Advancing pharmaceutical Intelligence via computationally Prognosticating the in-vitro parameters of fast disintegration tablets using Machine Learning models","authors":"Dhruv Gupta,&nbsp;Anuj A Biswas,&nbsp;Rohan Chand Sahu,&nbsp;Sanchit Arora,&nbsp;Dinesh Kumar,&nbsp;Ashish K Agrawal","doi":"10.1016/j.ejpb.2024.114508","DOIUrl":"10.1016/j.ejpb.2024.114508","url":null,"abstract":"<div><p>The field of Machine Learning (ML) has garnered significant attention, particularly in healthcare for predicting disease severity. Recently, the pharmaceutical sector has also adopted ML techniques in various stages of drug development. Tablets are the most common pharmaceutical formulations, with their efficacy influenced by the physicochemical properties of active ingredients, in-process parameters, and formulation components. In this study, we developed ML-based prediction models for disintegration time, friability, and water absorption ratio of fast disintegration tablets. The model development process included data visualization, pre-processing, splitting, ML model creation, and evaluation. We evaluated the models using root mean square error (RMSE) and R-squared score (R²). After hyperparameter tuning and cross-validation, the voting regressor model demonstrated the best performance for predicting disintegration time (RMSE: 21.99, R²: 0.76), surpassing previously reported models. The random forest regressor achieved the best results for friability prediction (RMSE: 0.142, R²: 0.7), and the K-nearest neighbor (KNN) regressor excelled in predicting the water absorption ratio (RMSE: 10.07, R²: 0.94). Notably, predicting friability and water absorption ratio using ML models is unprecedented in the literature. The developed models were deployed in a web app for easy access by anyone. These ML models can significantly enhance the tablet development phase by minimizing experimental iterations and material usage, thereby reducing costs and saving time.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114508"},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270678","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":"pH-Sensitive Tacrolimus loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease","authors":"Sidra Altaf ,&nbsp;Mahira Zeeshan ,&nbsp;Hussain Ali ,&nbsp;Ahmed Zeb ,&nbsp;Iqra Afzal ,&nbsp;Ayesha Imran ,&nbsp;Danish Mazhar ,&nbsp;Salman Khan ,&nbsp;Fawad Ali Shah","doi":"10.1016/j.ejpb.2024.114461","DOIUrl":"10.1016/j.ejpb.2024.114461","url":null,"abstract":"<div><div>Inflammatory Bowel Disease is the chronic tissue inflammation of the lower part of the Gastrointestinal tract (GIT). Conventional therapeutic approaches face numerous challenges, often making the delivery system inadequate for treating the disease. This study aimed to integrate a pH-sensitive polymer and nanostructured lipid carriers (NLCs) to develop a hybrid nanocarrier system. Tacrolimus-loaded NLCs coated with Eudragit® FS100 (TAC-NLCs/E FS100) nanoparticles were prepared via double emulsion technique followed by an aqueous enteric coating technique. Various parameters, such as particle size, entrapment efficiency, and zeta potential were optimized using Design Expert software®. Cetyltrimethyl ammonium bromide (CTAB) was used as a cationic surfactant which induces a positive charge on the nanoparticles. These cationic NLCs can adhere to the mucosal surface, thereby enabling prolonged retention. In vitro drug release was assessed, and the results demonstrated that drug release was retarded at pH 1.2 corresponding to upper GIT pH and maximum drug was released at pH 7.4 (colonic pH). Moreover, we evaluated TAC-NLCs/E FS100 nanoparticles in murine colitis models to gauge the efficacy of both coated and uncoated NLCs formulation. The TAC-NLCs/E FS100 showed a pronounced reduction in induced colitis, as evident from the restoration of morphological features, improved histopathological scores, antioxidant levels, and decreased the levels of proinflammatory cytokines. Thus, pH-sensitive TAC-NLCs/EFS 100 are attributed to the enhanced localization and targeted delivery at the specific site.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114461"},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282534","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":"Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug","authors":"Rick Heida ,&nbsp;Paulo H. Jacob Silva ,&nbsp;Renate Akkerman ,&nbsp;Jill Moser ,&nbsp;Jacqueline de Vries-Idema ,&nbsp;Aurélien Bornet ,&nbsp;Sujeet Pawar ,&nbsp;Francesco Stellacci ,&nbsp;Henderik W. Frijlink ,&nbsp;Anke L.W. Huckriede ,&nbsp;Wouter L.J. Hinrichs","doi":"10.1016/j.ejpb.2024.114507","DOIUrl":"10.1016/j.ejpb.2024.114507","url":null,"abstract":"<div><p>Increasing resistance to antiviral drugs approved for the treatment of influenza urges the development of novel compounds. Ideally, this should be complemented by a careful consideration of the administration route. 6′siallyllactosamine-functionalized β-cyclodextrin (CD-6′SLN) is a novel entry inhibitor that acts as a mimic of the primary attachment receptor of influenza, sialic acid. In this study, we aimed to develop a dry powder formulation of CD-6′SLN to assess its in vivo antiviral activity after administration via the pulmonary route. By means of spray drying the compound together with trileucine, a dispersion enhancer, we created a powder that retained the antiviral effect of the drug, remained stable under elevated temperature conditions and performed well in a dry powder inhaler. To test the efficacy of the dry powder drug against influenza infection in vivo, infected mice were treated with CD-6′SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6′SLN was effective in mitigating the course of the disease compared to the control groups, reflected by lower disease activity scores and by the prevention of virus-induced IL-6 production. Our data show that CD-6′SLN can be formulated as a stable dry powder that is suitable for use in a dry powder inhaler and is effective when administered via the pulmonary route to influenza-infected mice.</p></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114507"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003333/pdfft?md5=4d9f9df06c924b8074f1e7a658edf23a&pid=1-s2.0-S0939641124003333-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270679","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}

{"title":"Hydrophobic solid lipid-based microparticles for the protection of gastric-sensitive hydrophilic active biomolecules for oral administration in the treatment of EPI","authors":"Alexis Bages ,&nbsp;Mickaël Castelain ,&nbsp;Nicolas Dietrich ,&nbsp;Rosanne Raynal ,&nbsp;Karim Ioualalen","doi":"10.1016/j.ejpb.2024.114504","DOIUrl":"10.1016/j.ejpb.2024.114504","url":null,"abstract":"<div><div>Exocrine Pancreatic Insufficiency (EPI), induced by conditions such as cystic fibrosis, chronic pancreatitis, and Crohn’s disease, is a frequently overlooked and underdiagnosed gastrointestinal disorder. It leads to inadequate intestinal digestion due to insufficient secretion of pancreatic juice, resulting in discomfort, pain, and ultimately severe malnutrition. Despite numerous treatments proving ineffective over the past three decades, a strictly hydrophobic solid lipid formulation, administered orally, is proposed in this study to restore digestive function. This technology relies on the hydrophobic nature of the matrix to physically protect the hydrophilic active principle from the gastric environment while enabling its immediate release in the duodenum by targeting the amphiphilic nature of bile salts. Results demonstrate that this formulation effectively protects an acid-sensitive active ingredient during gastric passage (Simulated Gastric Fluid or SGF), facilitating its rapid release upon entering an artificial duodenal environment (Simulated Intestinal Fluid or SIF). Furthermore, it has been demonstrated that the preservation of a protein-based active ingredient extends beyond its primary protein structure to include its functional aspects, such as enzymatic activity. This drug delivery technology could enable the protection of hydrophilic active biomolecules, such as pancreatin, which are sensitive to gastric acidity, while promoting their immediate release upon contact with bile salts in the proximal duodenum, with the ultimate goal of correcting the digestive defect induced by EPI.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114504"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282517","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":"Enhanced photodynamic therapy of curcumin using biodegradable PLGA coated mesoporous silica nanoparticles","authors":"Muhammad Umair Amin ,&nbsp;Sajid Ali ,&nbsp;Konrad H. Engelhardt ,&nbsp;Usman Nasrullah ,&nbsp;Eduard Preis ,&nbsp;Jens Schaefer ,&nbsp;Josef Pfeilschifter ,&nbsp;Udo Bakowsky","doi":"10.1016/j.ejpb.2024.114503","DOIUrl":"10.1016/j.ejpb.2024.114503","url":null,"abstract":"<div><div>Since the available treatments are not highly effective to combat cancer, therefore, the alternative strategies are unavoidable. Photodynamic therapy (PDT) is one of the emerging approaches which is target specific and minimally invasive. This study explores the successful development of Poly (D,L-lactide-co-glycolide) (PLGA) coated mesoporous silica nanoparticles (MSNs) and their augmented effects achieved by integrating curcumin (Cur) and cetyltrimethylammonium bromide (CTAB) in the polymeric layer and silica’s pores, respectively. The synthesized nanocarriers (Cur-PLGA-cMSNs) have shown preferential targeting to the cellular organelles facilitated by CTAB’s and Cur’s affinity to mitochondria. CTAB and Cur-based PDT induced oxidative stress and generation of reactive oxygen species (ROS), resulting in dysfunctional mitochondria and triggered apoptotic pathways. PLGA coating has produced multifunctional effects, including; gatekeeping effects at pore openings, providing an extra loading site, enhancing the hemocompatibility of MSNs, and masking the free cur-related prolonged coagulation time. Cur-PLGA-cMSNs, as a multifaceted and combative approach with synergistic effects demonstrate promising potential to enhance outcomes in cancer treatment.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114503"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0939641124003291/pdfft?md5=4c737250f21726a79db9be66c1b4ad91&pid=1-s2.0-S0939641124003291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282516","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}