International Journal of Pharmaceutics最新文献

{"title":"Delivery of imiquimod to intestinal lymph nodes following oral administration","authors":"Haojie Chen ,&nbsp;Liuhang Ji ,&nbsp;Abigail Wong ,&nbsp;Yenju Chu ,&nbsp;Wanshan Feng ,&nbsp;Yufei Zhu ,&nbsp;Junting Wang ,&nbsp;Eleonora Comeo ,&nbsp;Dong-Hyun Kim ,&nbsp;Michael J. Stocks ,&nbsp;Pavel Gershkovich","doi":"10.1016/j.ijpharm.2024.124895","DOIUrl":"10.1016/j.ijpharm.2024.124895","url":null,"abstract":"<div><div>Intestinal lymph nodes are involved in the progression of colorectal cancer (CRC). Tumours suppress the activation of dendritic cells (DCs) in draining lymph nodes, diminishing anti-cancer immune response. Imiquimod (IMQ) facilitates DCs activation <em>via</em> toll-like receptor 7, suggesting that targeted delivery of IMQ to intestinal lymph nodes can improve the treatment of CRC. This study aims to enhance the delivery of IMQ to intestinal lymph nodes by a highly lipophilic prodrug approach. Amide prodrugs were synthesised by conjugating IMQ with saturated and unsaturated medium- to long-chain fatty acids. Their potential for intestinal lymphatic transport was assessed by their affinity to chylomicrons and solubility in long-chain triglycerides. Further selection of prodrug candidates was determined by resistance to enzymatic hydrolysis in intestinal lumen and release of IMQ in the lymphatics using fasting state simulated intestinal fluid supplemented with esterases, brush border enzyme vesicles and plasma. Key pharmacokinetic parameters and biodistribution in rats were assessed for the most promising compounds, prodrugs 5 and 8. The plasma concentration–time profile of IMQ following oral administration of the prodrugs was less erratic in comparison to the administration of unmodified IMQ. The lymph-to-plasma ratios of IMQ concentration increased 1.9- and 1.7-fold using prodrugs 5 and 8 in comparison to administration of unmodified IMQ, respectively. Importantly, the average concentration of IMQ in mesenteric lymph nodes (MLN) was 11.2- and 7.6-fold higher than in plasma following the administration of prodrugs 5 and 8, respectively. Additionally, the non-specific wide distribution of IMQ into various organs and tissues was reduced with prodrugs. This work suggests that the highly lipophilic prodrug approach can efficiently deliver IMQ to intestinal lymphatics. In addition, this study demonstrates the feasibility of an amide prodrug approach for intestinal lymphatic targeting.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124895"},"PeriodicalIF":5.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564191","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":"Innovative cancer therapy: Unleashing the potential of macromolecule-loaded mesoporous bioactive glasses for precision diagnosis and treatment","authors":"Ali Mohammad Amani ,&nbsp;Lobat Tayebi ,&nbsp;Ehsan Vafa ,&nbsp;Reza Bazargan-Lari ,&nbsp;Milad Abbasi ,&nbsp;Ahmad Vaez ,&nbsp;Hesam Kamyab ,&nbsp;Lalitha Gnanasekaran ,&nbsp;Shreeshivadasan Chelliapan ,&nbsp;Mohammad Javad Azizli","doi":"10.1016/j.ijpharm.2024.124847","DOIUrl":"10.1016/j.ijpharm.2024.124847","url":null,"abstract":"<div><div>Cancer continues to pose a formidable threat, claiming millions of lives annually. A beacon of hope in this battle lies in the realm of bioactive glasses, which have undergone a remarkable evolution over the past five decades. Among these, mesoporous bioactive glasses (MBGs) emerge as a dynamic subset endowed with customizable attributes such as high surface area and porosity. While holding immense promise for cancer care, the full clinical potential of MBGs remains largely unexplored. This review delves into the cutting-edge advancements in MBG technology, illuminating their pivotal role in cancer management – spanning from early detection to targeted therapeutic interventions like photothermal and photodynamic treatments. Furthermore, the molecular mechanisms underpinning MBGs’ anticancer properties are elucidated, alongside an exploration of existing limitations in their application. Through this comprehensive synthesis, the significance of MBGs in revolutionizing cancer therapy is underscored, underscoring the urgent need for continued research to unlock their full potential in reshaping the landscape of cancer care.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124847"},"PeriodicalIF":5.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564193","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":"Advancement in the nose-to-brain drug delivery of FDA-approved drugs for the better management of depression and psychiatric disorders.","authors":"Rajshekher Upadhyay, Pappu Ghosh, Madhuri Desavathu","doi":"10.1016/j.ijpharm.2024.124866","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124866","url":null,"abstract":"<p><p>The Prevalence of Depressive and Psychiatric disorders is increasing globally, and despite the availability of numerous FDA-approved drugs, treatment remains challenging. Many conventional antidepressants and antipsychotic formulations face issues such as low solubility, high first-pass metabolism, poor bioavailability, inadequate blood-brain barrier penetration, and systemic side effects. These challenges lead to reduced efficacy, slower onset of action, and decreased patient adherence to treatment. To address these problems, recent studies have explored the nose-to-brain route for drug delivery. This method offers several advantages, including non-invasive drug administration, direct access to the brain, rapid onset of action, reduced systemic exposure and side effects, avoidance of first-pass metabolism, enhanced bioavailability, precision dosing, and improved patient compliance. The formulations used for this approach include lipidic nanoparticles, polymeric nanoparticles, nasal gels, cubosomes, niosomes, polymeric micelles, nanosuspensions, nanoemulsions, nanocapsules, and elastosomes. This review analyzes and summarizes the published work on the nose-to-brain delivery of FDA-approved antidepressants and antipsychotic drugs, with a focus on the preparation, characterization, pharmacokinetics, pharmacodynamics, and toxicity profiling of these nanoformulations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124866"},"PeriodicalIF":5.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564190","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":"Nanostructured biloalbuminosomes loaded with berberine and berberrubine for Alleviating heavy Metal-Induced male infertility in rats","authors":"Aya M. Helal ,&nbsp;Mona M. Yossef ,&nbsp;Inas K. Seif ,&nbsp;Mohamed Abd El-Salam ,&nbsp;Maha A. El Demellawy ,&nbsp;Shaymaa A. Abdulmalek ,&nbsp;Ahmed Z. Ghareeb ,&nbsp;Jasmine Holail ,&nbsp;Abdulaziz Mohsen Al-mahallawi ,&nbsp;Sally A. El-Zahaby ,&nbsp;Doaa A Ghareeb","doi":"10.1016/j.ijpharm.2024.124892","DOIUrl":"10.1016/j.ijpharm.2024.124892","url":null,"abstract":"<div><div>Despite the remarkable biological effects of berberine (BBR), particularly on fertility, its bioavailability is low. This study aims to test the effectiveness of novel nanostructured biloalbuminosomes (BILS) of BBR and its metabolite berberrubine (M1) in treatment of testicular and prostatic lesions. M1 was semi-synthesized from BBR using microwave-assisted reaction. The solvent evaporation method was used to prepare BBR-BILS and M1-BILS by three different concentrations of sodium cholate (SC) or glycocholate (SG), along with the incorporation of bovine serum albumin (BSA). The prepared BILS were fully characterized. Male infertility was induced by cadmium (Cd) at 5 mg/kg and lead (Pb) at 20 mg/kg contaminated water for 90 days, followed by treatment with BBR, M1, and their BILS (BBR-BILS and M1-BILS) for 45 days. Blood male infertility markers, testicular and prostatic oxidative stress status, autophagy, inflammation, along with testicular and prostatic concentrations of Cd and Pb, and histopathology of both tested tissues were determined using standardized protocols. The optimal BBR-BILS and M1-BILS nano-preparations, containing 30 mg SC, were chosen based on the best characterization properties of the preparations. Both nano-preparations improved heavy metals-induced testicular and prostatic deformities, as they reduced Bax and elevated Bcl-2 expressions in both tissues. Moreover, they activated the mTOR/PI3K pathway with a marked reduction in AMPK and activated LC-3II protein levels. Consequently, testicular and prostatic architecture and functions were improved. This study is the first to report the preparation of BBR and M1 BILS nano-preparations and proved their superior efficacy compared to free drugs against testicular and prostatic deformities by attenuating oxidative stress-induced excessive autophagy, offering a new hope to manage male infertility.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124892"},"PeriodicalIF":5.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557827","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":"Computer-Aided formulation design for pharmaceutical drug product development, part 01: Materials exploration through a visualization tool.","authors":"Patrick M Piccione, Moritz N Lang, Felipe Amado Becker, Albert Hofstetter, Stéphanie Marchal, Kevin Ly, Valentin Legras, Andreas Ewert, David Kohler, Reto Maurer, Nina Willecke, Ryan Burwood, Paul Kroll","doi":"10.1016/j.ijpharm.2024.124891","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124891","url":null,"abstract":"<p><p>An interactive tool has been developed to help design oral solid dosage form formulations. The tool enables quantitative explorations and comparisons of physical, bulk, and mechanical properties, and takes into account functional characteristics as well. In this manner, comparisons and clustering of both excipients and APIs can be carried out. These comparisons enable the generation of alternatives as well as surrogate identification, so as to spare resources and material. Multiple data sources were merged to create a \"joint\" data table with all relevant properties. Four main workflow activities are supported: Explore Materials, Search Similar APIs, Search Similar Excipients and Search Material Clusters. Multi-dimensional filtering can be superimposed to each functionality. Suggested visualizations are made particularly accessible by providing them as \"standard plots\". The underlying philosophy is to empower formulation scientists to explore options, rather than prescribe decisions on exclusively mathematical grounds. The tool described here is the first step towards a holistic optimization incorporating predictions of mixture properties. Methodology of use is illustrated through three material selection application examples.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"124891"},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557824","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":"Metal ion formulations for diabetic wound healing: Mechanisms and therapeutic potential","authors":"Yuhe Dai ,&nbsp;Qianbo Zhang ,&nbsp;Rifang Gu ,&nbsp;Jitao Chen ,&nbsp;Penghui Ye ,&nbsp;Huan Zhu ,&nbsp;Ming Tang ,&nbsp;Xuqiang Nie","doi":"10.1016/j.ijpharm.2024.124889","DOIUrl":"10.1016/j.ijpharm.2024.124889","url":null,"abstract":"<div><div>Metals are vital in human physiology, which not only act as enzyme catalysts in the processes of superoxide dismutase and glucose phosphorylation, but also affect the redox process, osmotic adjustment, metabolism and neural signals. However, metal imbalances can lead to diseases such as diabetes, which is marked by chronic hyperglycemia and affects wound healing. The hyperglycemic milieu of diabetes impairs wound healing, posing significant challenges to patient quality of life. Wound healing encompasses a complex cascade of hemostasis, inflammation, proliferation, and remodeling phases, which are susceptible to disruption in hyperglycemic conditions. In recent decades, metals have emerged as critical facilitators of wound repair by enhancing antimicrobial properties (e.g., iron and silver), providing angiogenic stimulation (copper), promoting antioxidant activity and growth factor synthesis (zinc), and supporting wound closure (calcium and magnesium). Consequently, research has pivoted towards the development of metal ion-based therapeutics, including innovative formulations such as nano-hydrogels, nano-microneedle dressings, and microneedle patches. Prepared by combining macromolecular materials such as chitosan, hyaluronic acid and sodium alginate with metals, aiming at improving the management of diabetic wounds. This review delineates the roles of key metals in human physiology and evaluates the application of metal ions in diabetic wound management strategies.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124889"},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557826","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":"Launching triple-hit chemo attack on TNBC through nanoparticle-mediated codelivery of cisplatin-chlorambucil conjugate and venetoclax","authors":"Tushar Date,&nbsp;Oly Katari,&nbsp;Kaushik Kuche,&nbsp;Dasharath Chaudhari,&nbsp;Sanyog Jain","doi":"10.1016/j.ijpharm.2024.124890","DOIUrl":"10.1016/j.ijpharm.2024.124890","url":null,"abstract":"<div><div>The BRCA1 dysfunction and HR deficiency in TNBC are responsible for high effectiveness of DNA-damaging agents in TNBC treatment. Preclinical and clinical studies confirmed the effectiveness of cisplatin in TNBC treatment. Nevertheless, the clinical utility of cisplatin is inadequate due to severe systemic side effects and resistance development. Dual-action cisplatin (IV) prodrugs provide an excellent opportunity to improve anticancer activity, reduce toxicities and minimize chance of resistance development. Therefore, in this investigation we have synthesized cisplatin-chlorambucil (CP-CBL) prodrug and loaded it with venetoclax (VTX) in phenylboronic acid conjugated TPGS-lactide nanoparticles (TNPs) to achieve tumor-targeted drug delivery thereby reducing the therapeutic dose as well as increasing the efficacy of free cisplatin, chlorambucil and venetoclax. The TNPs possessed particle size of 143 nm, PDI 0.186 and entrapment efficiency of 63.5 % and 56.4 % for VTX and CP-CBL. The TNPs followed Higuchi release kinetic model and represented biphasic release behaviour with early burst release of drug within 2 h succeeded by sustained drug release till 72 h. Further, the TNPs showed ∼ 42 folds and ∼ 19 folds reduction in the IC₅₀ values compared to free CP. Also, higher cellular uptake and therefore greater apoptotic index was observed for the TNPs in comparison to the untargeted nanoparticles. The TNPs further showed higher ROS generating potential, enhanced mitochondrial membrane depolarization, higher intensity of nuclear condensation and highest level of caspase-3 expression. Moreover, a noteworthy decrease in the tumor volume was noticed in the mice treated with TNPs along with lower serum toxicity biomarker levels compared to the free drugs. Overall, the developed TNPs proved to be a promising and safer strategy for inducing triple-hit action in TNBC management.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124890"},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557825","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":"Autoinjector optimization through cavitation response and severity minimization","authors":"Tyler R. Kennelly,&nbsp;Sadegh Dabiri","doi":"10.1016/j.ijpharm.2024.124888","DOIUrl":"10.1016/j.ijpharm.2024.124888","url":null,"abstract":"<div><div>Abrupt acceleration of the syringe of an autoinjector (AI) upon rod-plunger impact may induce undesired severe cavitation events and impose extraneous stresses upon the device, leading to device failure. Cavitation results from a rapid and significant pressure drop in a liquid, leading to the formation and growth of small vapor-filled cavities. Upon collapse, these cavities generate an intense shock wave that may lead to protein aggregation and device container damage and shatter. Since the maximum acceleration of the syringe depends upon the operating conditions of the AI, the severity of cavitation will likewise depend on the operating conditions of the AI. Likewise, injection time and ensuring proper needle displacement before drug release also depend on operating conditions, making optimization of the autoinjector a multiobjective optimization problem.</div><div>Therefore, in this study, optimization of an autoinjector to limit cavitation severity is pursued via an experimentally validated computational model for cavitation in spring-driven autoinjectors. Our goal is to locate AI design configurations that balance maximizing device performance and patient comfort and minimizing the risks of device damage and severe cavitation upon actuation.</div><div>Relevant parameters of interest are the drive spring force, air gap height, solution viscosity, friction between the rod and spring, frictional force on the plunger, rates of change of frictional force on the plunger, elasticity of plunger, viscosity of the plunger, and initial displacement between the plunger and the driving rod. The kinematics of the syringe barrel, needle displacement (travel distance) at the start of drug delivery, and injection time are gathered using an experimentally validated autoinjector kinematics model. At the same time, cavitation bubble dynamics are resolved using an experimentally validated cavitation model that takes the temporal displacement of the syringe and temporal air gap pressure as inputs.</div><div>We use our experimentally validated models to explore the parameter space and understand the driving factors of our desired outcomes. Subsequently, we pose the design problem as a multi-objective optimization problem and develop a deep neural network surrogate model supplemented with iterative learning to speed up optimization. A variance-based sensitivity analysis was performed to determine the sensitivity and influence of design parameters on the outcomes, and the main contributors to the outcomes of interest were isolated. Using a multi-objective optimization framework, we located 300 + successful candidates and evaluated them through uncertainty analysis to identify three promising candidates that meet all criteria for drug viscosities of interest. Finally, we show that this methodology can be used to conduct hypothesis testing, leading to novel design configurations.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124888"},"PeriodicalIF":5.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557823","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":"Biochanin-A co-crystal formulation improves bioavailability and ameliorates cerulein-induced pancreatitis by attenuating the inflammation","authors":"Hari Priya Sripadi ,&nbsp;Rajwinder Kaur ,&nbsp;Saylee Manohar Koli ,&nbsp;Nidhi Sharma ,&nbsp;Vijaya Sarathi U.V.R. ,&nbsp;Jagadeesh Babu Nanubolu ,&nbsp;Sai Balaji Andugulapati ,&nbsp;Ramakrishna Sistla","doi":"10.1016/j.ijpharm.2024.124874","DOIUrl":"10.1016/j.ijpharm.2024.124874","url":null,"abstract":"<div><div>Co-crystallization of a therapeutic ingredient with an appropriate co-former is a powerful technique to augment the physicochemical and pharmacokinetic properties and the effectiveness of Active Pharmaceutical Ingredients (APIs). Biochanin A (BCA), a flavonoid with medicinal potential, is limited by poor solubility and low oral bioavailability. This study aimed to design and develop a novel BCA-nicotinamide cocrystal as BCC to enhance BCA’s oral bioavailability and explore its therapeutic potential for ameliorating cerulein-induced acute pancreatitis (CIAP) by elucidating the target identification utilizing tissue/serum metabolite profiles. The cocrystal was designed by the supramolecular synthon approach and characterized by single-crystal X-ray diffraction that confirms a robust three-dimensional hydrogen-bonded network of BCA and Nicotinamide (NCT) in the crystal. FT-IR and DSC were used to analyze the cocrystal’s intermolecular interactions and thermal behavior. BCC exhibited enhanced solubility and drug release compared to BCA alone, resulting in enhanced oral bioavailability and pancreatic tissue concentration. Comparing BCC to BCA in the CIAP model, BCC therapy remarkably reduced cerulein-induced pancreatitis, evidenced by significant reductions in inflammation, acinar cell atrophy, and amylase levels in pancreatic tissues. Further, the cocrystal formulation also down-regulated the oxidative stress markers, inflammatory cytokines and macrophage-related proteins. The study has identified distinct metabolomic signatures linked with AP with the help of Orbitrap Exploris mass spectrometry, which could pave the way for creating focused diagnostic tools for a better prognosis. In conclusion, these results offer new insights into exploring mechanistic pathways associated with specific biomarkers and underscore BCC cocrystal as a promising approach to enhance BCA’s therapeutic potential.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124874"},"PeriodicalIF":5.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568839","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":"Vasculo-osteogenic keratin-based nanofibers containing merwinite nanoparticles and sildenafil for bone tissue regeneration","authors":"Basma Talib Al-Sudani ,&nbsp;Mastafa H. Al-Musawi ,&nbsp;Marwa M. Kamil ,&nbsp;Sumyah H. Turki ,&nbsp;Sepideh Nasiri- Harchegani ,&nbsp;Aliakbar Najafinezhad ,&nbsp;Parastoo Noory ,&nbsp;Sina Talebi ,&nbsp;Hamideh Valizadeh ,&nbsp;Fariborz Sharifianjazi ,&nbsp;Leila Bazli ,&nbsp;Mohamadreza Tavakoli ,&nbsp;Morteza Mehrjoo ,&nbsp;Mahboubeh Firuzeh ,&nbsp;Marjan Mirhaj","doi":"10.1016/j.ijpharm.2024.124875","DOIUrl":"10.1016/j.ijpharm.2024.124875","url":null,"abstract":"<div><div>Vascularization of bone tissue constructs plays a pivotal role in facilitating nutrient transport and metabolic waste removal during the processes of osteogenesis and bone regeneration <em>in vivo</em>. In this study, a sildenafil (Sil)-loaded nanofibrous scaffold of keratin/Soluplus/merwinite (KS.Me.Sil) was fabricated through electrospinning and the effectiveness of the scaffold was assessed for bone tissue engineering applications. The KS.Me.Sil nanofibrous scaffold exhibited notably enhanced ultimate tensile strength (3.38 vs 2.61 MPa) and elastic modulus (69.83 vs 46.27 MPa) compared to the KS scaffold. The <em>in vitro</em> release of Ca²⁺, Si⁴⁺ and Mg²⁺ ions and the release of Sil from the nanofibers as well as biodegradability and bioactivity were evaluated for 14 days. Protein adsorption capability and cytocompatibility of the scaffolds were tested. Alkaline phosphatase activity test, Alizarin red staining and qRT-PCR analysis demonstrated that the KS.Me.Sil nanofibers had the best osteogenic activity among other samples. Also, the results of the chorioallantoic membrane assay showed an almost threefold increase in blood vessel density in the group treated with the KS.Me.Sil nanofibers extract compared to the KS. In conclusion, our findings suggest that the electrospun KS.Me.Sil nanofibrous scaffold offers a robust structure with exceptional osteogenic and angiogenic characteristics, making it a promising candidate for bone tissue engineering applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124875"},"PeriodicalIF":5.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545405","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}