Advanced pharmaceutical bulletin最新文献

{"title":"Development of Gentamicin Bilosomes Laden <i>In Situ</i> Gel for Topical Ocular Delivery: Optimization, <i>In Vitro</i> Characterization, Toxicity, and Anti-microbial Evaluation.","authors":"Ameeduzzafar Zafar, Omar Awad Alsaidan, Malik Suliman Mohamed, Mohd Yasir, Mohammad Khalid","doi":"10.34172/apb.2024.057","DOIUrl":"10.34172/apb.2024.057","url":null,"abstract":"<p><strong>Purpose: </strong>The eye drops are the prominent preparation used to treat surface eye disease (bacterial conjunctivitis). However, they have some limitations i.e., short corneal residence, resulting in low ocular bioavailability and necessitating frequent dose administration. The present study developed gentamicin (GE) bilosomes (BM)- laden <i>in situ</i> gel to improve therapeutic activity. The <i>in situ</i> gel system is initially in sol form before administration and converted into gel form in physiological eye conditions.</p><p><strong>Methods: </strong>The GE-BM was developed using the thin film hydration technique and optimized by D-optimal design. GE-BM was characterized for vesicle size, entrapment efficiency, zeta potential, morphology, and Fourier transform electron microscope (FTIR). The optimized GE-BM (GE-BMopt) was incorporated into an <i>in situ</i> gel and assessed for physicochemical characteristics. GE-BMopt <i>in situ</i> gel was evaluated for <i>in vitro</i> release, <i>ex vivo</i> permeation, toxicity, and antimicrobial study.</p><p><strong>Results: </strong>GE-BMopt has a vesicle size of 185.1±4.8nm, PDI of 0.254, zeta potential of 27.6 mV, entrapment efficiency of 81.86±1.29 %, and spherical morphology. The FTIR study presented no chemical interactions between GE and excipients. GE-BMopt <i>in situ</i> gel (GE-BMoptIG4) showed excellent viscosity, gelling strength, and <i>ex-vivo</i> bio-adhesion. GE-BMopt-IG4 showed significant high and sustained release of GE (78.08±4.73% in 12h). GE-BMopt-IG4 displayed 3.27-fold higher <i>ex-vivo</i> goat corneal permeation than a pure GE solution. GE-BMopt-IG4 showed good corneal tolerance without any damage or irritation. GE-BMopt-IG4 showed significantly (<i>P</i><0.05) higher anti-bacterial activity (ZOI) against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> than pure GE solution.</p><p><strong>Conclusion: </strong>The study determined that the BM <i>in situ</i> gel system can serve as a substitute carrier for GE to enhance its therapeutic effectiveness, and further preclinical studies are required.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"646-664"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLC Delivery of EGFP Plasmid to TM4 Cell Nuclei for Targeted Gene Therapy.","authors":"Nurul Jummah, Satrialdi Satrialdi, Aluicia Anita Artarini, Anindyajati Anindyajati, Diky Mudhakir","doi":"10.34172/apb.2024.050","DOIUrl":"10.34172/apb.2024.050","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluated whether a nanostructured lipid carrier (NLC) delivery system could safely and accurately deliver nucleic acids to the cell nucleus using the enhanced green fluorescent protein (EGFP)-C1 plasmid model.</p><p><strong>Methods: </strong>The NLC was formulated using the emulsification method and equipped for cationic lipid-mediated transfection with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), which interacts electrostatically with nucleic acid. The NLC attributes, including size, polydispersity index, and zeta potential, were assessed by dynamic light scattering (DLS). The morphological structure was analyzed using transmission electron microscopy. Entrapment efficiency was evaluated by a direct method. Cellular uptake mechanisms of pEGFP-C1-NLC and the ability of pEGFP-C1 to penetrate the nucleus of TM4 cells to express EGFP were observed using confocal microscopy.</p><p><strong>Results: </strong>pEGFP-C1-NLC exhibited particle sizes in the range 56-88 nm with a particle charge range of -6.0 to+1.3 mV. The polydispersity index<0.5 showed good size uniformity, and entrapment efficiency of pEGFP-C1in the NLC was 92.06±2.295%. The NLC formulation was internalized predominantly via caveolae-mediated endocytosis, as indicated by EGFP expression following successful delivery of pEGFP by the NLC into the cells.</p><p><strong>Conclusion: </strong>NLC formulation could deliver genetic material to the nucleus and could be considered a gene therapy candidate for spermatogenesis.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"613-622"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Menadione Sodium Bisulfite Loaded Rhamnolipid Based Solid Lipid Nanoparticle as Skin Lightener Formulation: A Green Production Beside In Vitro/In Vivo Safety Index Evaluation.","authors":"Fatemeh Asadpour Panbehchouleh, Hossein Amani, Majid Saeedi","doi":"10.34172/apb.2024.047","DOIUrl":"10.34172/apb.2024.047","url":null,"abstract":"<p><strong>Purpose: </strong>In the current investigation, an ultrasonic approach was performed to produce menadione sodium bisulfite-loaded solid lipid nanoparticles (MSB-SLNs) with rhamnolipid as bio-surfactant, which aimed to increase the dermal delivery and anti-pigmentation effect.</p><p><strong>Methods: </strong>To achieve optimum delivery for MSB, the impact of the ratio of two surfactants (rhamnolipid: Tween) on nanoparticle attributes and the respective functions were evaluated. In vitro diffusion process, in vitro cytotoxicity assay, determination of melanin content of melanoma cells, L-DOPA auto-oxidation inhibitory test, and skin irritation studies carried out to investigate the suitability of MSB formulation in dermal application.</p><p><strong>Results: </strong>The optimized nanoparticles showed an average particle size, zeta potential, polydispersity index (PDI), and drug entrapment efficiency of 117.26±1.12 nm, -6.28±0.33 mV, 0.262±0.002, 83.34±0.75% respectively in hydrophilic-lipophilic balance (HLB) of 12. The in vitro diffusion process demonstrated that MSB-SLN gel had a prolonged release pattern. The levels of MSB in the cutaneous layers (52.192±2.730% or 961.59±50.313 μg/cm² ) and the receiver compartment (23.721±1.803 % or 437.049± 33.236 μg/cm² ) for the MSB-SLN gel was higher than MSB simple and showed no cutaneous irritancy and toxicity in rats. MSB-SLN inhibited melanin formation and was remarkably higher than free MSB. MSB-SLN inhibited L-3,4- dihydroxyphenylalanine (L-DOPA) auto-oxidation to a greater extent (95.14±1.46%) than MSB solution (72.28±0.83%).</p><p><strong>Conclusion: </strong>This study's observations revealed that the produced MSB-SLN might be used as a potential nano-vehicle for MSB dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"623-633"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Interplay between the Warburg Effect and Glucolipotoxicity in Cancer Development: A Novel Perspective on Cancer Etiology.","authors":"Maher Monir Akl, Amr Ahmed","doi":"10.34172/apb.2024.049","DOIUrl":"10.34172/apb.2024.049","url":null,"abstract":"<p><p>The Warburg effect, first observed by Otto Warburg in the 1920s, delineates a metabolic phenomenon in which cancer cells exhibit heightened glucose uptake and lactate production, even under normoxic conditions. This metabolic shift towards glycolysis, despite the presence of oxygen, fuels the energy demands of rapidly proliferating cancer cells. Dysregulated glucose metabolism, characterized by the overexpression of glucose transporters and the redirection of metabolic pathways towards glycolysis, lies at the crux of this metabolic reprogramming. Consequently, the accumulation of lactate as a byproduct contributes to the creation of an acidic tumor microenvironment, fostering tumor progression and metastasis. However, recent research, notably proposed by Maher Akl, introduces a novel perspective regarding the role of glycolipids in cancer metabolism. Akl's glucolipotoxicity hypothesis posits that aberrant glycolipid metabolism, specifically the intracellular buildup of glycolipids, significantly influences tumor initiation and progression. This hypothesis underscores the disruptive impact of accumulated glycolipids on cellular homeostasis, thereby activating oncogenic pathways and promoting carcinogenesis. This perspective aims to synthesize the intricate mechanisms underlying both the Warburg effect and glucolipotoxicity, elucidating their collective contributions to tumor growth and malignancy. By comprehensively understanding these metabolic aberrations, novel avenues for therapeutic intervention targeting the fundamental drivers of cancer initiation and progression emerge, holding promise for more efficacious treatment strategies in the future.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"705-713"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomedicine Strategies Utilizing Lipid-Based Nanoparticles for Liver Cancer Therapy: Exploring Signaling Pathways and Therapeutic Modalities.","authors":"Fereshteh Asgharzadeh, Maryam Moradi Binabaj, Sahar Fanoudi, William C Cho, Yu-Jeong Yang, Maryam Azarian, Mehdi Shafiee Ardestani, Nasim Nasiri, Marzieh Ramezani Farani, Yun Suk Huh","doi":"10.34172/apb.2024.061","DOIUrl":"10.34172/apb.2024.061","url":null,"abstract":"<p><p>Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths, following pancreatic cancer. The 5-year overall survival rate for HCC remains relatively low. Currently, there are multiple treatment options available for HCC, including systemic drugs, minimally invasive local therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), and arterial radioembolization (TARE), as well as surgical interventions like liver resection or transplantation. However, the effectiveness of drug delivery to the cancerous liver is hindered by pathophysiological changes in the organ. In order to address this challenge, lipid-based nanoparticles (LNPs) have emerged as promising platforms for delivering a diverse range of therapeutic drugs. LNPs offer various structural configurations that enhance their physical stability and enable them to accommodate different types of cargo with varying mechanical properties and degrees of hydrophobicity. In this article, we provide a comprehensive review of the current applications of LNPs in the development of anti-HCC therapies. By examining the existing research, we aim to shed light on the potential future directions and advancements in this field.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"513-523"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Functional and Folding Stability of an Engineered <i>E. coli</i> L-asparaginase Harboring Y176F/S241C Mutations.","authors":"Mahrokh Dastmalchi, Maryam Hamzeh-Mivehroud, Hassan Rezazadeh, Mohammad M Farajollahi, Siavoush Dastmalchi","doi":"10.34172/apb.2024.048","DOIUrl":"10.34172/apb.2024.048","url":null,"abstract":"<p><strong>Purpose: </strong>L-asparaginase has been widely recognized as a critical component in the treatment of various types of lymphoproliferative disorders, since its introduction in 1960s. However, its use in some cases leads to allergic reactions rendering the continuation of treatment unfeasible. Thus, the development of L-asparaginase from alternative sources or the production of engineered enzymes have always been considered. This study aimed to produce and evaluate a novel enzyme designed based on the sequence of L-asparaginase from <i>Escherichia coli</i> bacteria with Y176F/S241C mutations.</p><p><strong>Methods: </strong>The Y176F/S241C mutant L-asparaginase was successfully expressed as the GST-fusion protein in <i>E. coli</i>, and then was subjected to affinity and size exclusion chromatography. The activity of the purified enzyme was determined based on the released ammonia as the result of substrate hydrolysis using Nessler's reagent. Chemical denaturation experiment in the presence of increasing concentration of guanidinium chloride was applied to determine the folding stability of the purified enzyme.</p><p><strong>Results: </strong>The mutant enzyme was purified with an efficiency of 77-fold but at a low recovery of 0.7%. The determined kinetic parameters Km, Vmax, kcat, specific activity and catalytic efficiency were 13.96 (mM), 2.218 (mM/min), 273.9 (min^-1), 237.8 (IU/mg) and 19.62 (mM^-1 min^-1), respectively. Moreover, unfolding free energy determined by guanidinium chloride induced denaturation for mutated and commercial L-asparaginase enzymes were 8421 J/mol and 5274 J/mol, respectively.</p><p><strong>Conclusion: </strong>The mutant enzyme showed improved stability over the wild-type. Although the expression level and recovery were low, the mutant L-asparaginase demonstrated promising activity and stability, with potential clinical and industrial applications.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"675-685"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-stage Acting Dendrimeric Nanoparticle for Deepened Chemotherapeutic Drug Delivery to Tumor Cells.","authors":"Mohammad Shahpouri, Mohammad Amin Adili-Aghdam, Hossein Mahmudi, Saeedeh Ghiasvand, Hamed Dadashi, Aysan Salemi, Sajjad Alimohammadvand, Leila Roshangar, Abolfazl Barzegari, Mehdi Jaymand, Rana Jahanban-Esfahlan","doi":"10.34172/apb.2024.054","DOIUrl":"10.34172/apb.2024.054","url":null,"abstract":"<p><strong>Purpose: </strong>We report on the design of hypoxia-induced dual-stage acting dendrimeric nanoparticles (NPs) for selective delivery of two chemotherapeutic model drugs doxorubicin (DOX) and tirapazamin (TPZ) for deepened drug delivery into hypoxic tumors <i>in vitro</i>.</p><p><strong>Methods: </strong>PAMAM G5 dendrimers were crosslinked with a hypoxic azo linker, attached to a mPEG to form a detachable corona on the dendrimer surface (PAP NPs). NPs were characterized by Zeta sizer, transmission electron microscope (TEM), Fourier transforms infrared (FTIR) and drug release kinetics. The anti-cancer performance of PAPs was evaluated by numerous tests in 2D and 3D cultured MDA-MB-231 breast cancer cells.</p><p><strong>Results: </strong>MTT assay showed a significant difference between PAP and PAMAMG5 in terms of biocompatibility, and the effect of PAP@DOX was significantly greater than free DOX in hypoxic conditions. The results of DAPI and Annexin V-FITC/PI cell staining also confirmed uniform drug penetration as validated by induction of 90% cell apoptosis in spheroids and a high level of PAP@DOX-induced ROS generation under hypoxia conditions. Mechanistically, PAP@DOX significantly reduced the expression of mTOR, and Notch1, while the expression of Bax and Caspase3 was considerably unregulated, compared to the controls. Importantly, hypoxia-responsive disintegration and hypoxia-induced activation of HAP drug were synergized to promote deep and homogenous HAP distribution in whole microtumor regions to efficiently eliminate residual tumor cells.</p><p><strong>Conclusion: </strong>Our results indicate the safety and high therapeutic potential of PAP system for targeted drug delivery of chemotherapeutics in particular HAPs which show maximum anti-cancer activity against hypoxic solid tumors.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"634-645"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Accuracy of Large Language Model (ChatGPT) in Providing Information on Metastatic Breast Cancer.","authors":"Ramakrishna Gummadi, Nagasen Dasari, D Sathis Kumar, Sai Kiran S S Pindiprolu","doi":"10.34172/apb.2024.060","DOIUrl":"10.34172/apb.2024.060","url":null,"abstract":"<p><strong>Purpose: </strong>Artificial intelligence (AI), particularly large language models like ChatGPT developed by OpenAI, has demonstrated potential in various domains, including medicine. While ChatGPT has shown the capability to pass rigorous exams like the United States Medical Licensing Examination (USMLE) Step 1, its proficiency in addressing breast cancer-related inquiries-a complex and prevalent disease-remains underexplored. This study aims to assess the accuracy and comprehensiveness of ChatGPT's responses to common breast cancer questions, addressing a critical gap in the literature and evaluating its potential in enhancing patient education and support in breast cancer management.</p><p><strong>Methods: </strong>A curated list of 100 frequently asked breast cancer questions was compiled from Cancer.net, the National Breast Cancer Foundation, and clinical practice. These questions were input into ChatGPT, and the responses were evaluated for accuracy by two primary experts using a four-point scale. Discrepancies in scoring were resolved through additional expert review.</p><p><strong>Results: </strong>Of the 100 responses, 5 were entirely inaccurate, 22 partially accurate, 42 accurate but lacking comprehensiveness, and 31 highly accurate. The majority of the responses were found to be at least partially accurate, demonstrating ChatGPT's potential in providing reliable information on breast cancer.</p><p><strong>Conclusion: </strong>ChatGPT shows promise as a supplementary tool for patient education on breast cancer. While generally accurate, the presence of inaccuracies underscores the need for professional oversight. The study advocates for integrating AI tools like ChatGPT in healthcare settings to support patient-provider interactions and health education, emphasizing the importance of regular updates to reflect the latest research and clinical guidelines.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 3","pages":"499-503"},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Hidden Menace: A Topic Modeling Analysis of Hijacked Medical Journals.","authors":"Mehdi Dadkhah, Mihály Hegedűs, Prema Nedungadi, Raghu Raman, Lóránt Dénes Dávid","doi":"10.34172/apb.2024.029","DOIUrl":"10.34172/apb.2024.029","url":null,"abstract":"<p><strong>Purpose: </strong>Nowadays, many studies discuss scholarly publishing and associated challenges, but the problem of hijacked journals has been neglected. Hijacked journals are cloned websites that mimic original journals but are managed by cybercriminals. The present study uses a topic modeling approach to analyze published papers in hijacked versions of medical journals.</p><p><strong>Methods: </strong>A total of 3384 papers were downloaded from 21 hijacked journals in the medical domain and analyzed by topic modeling algorithm.</p><p><strong>Results: </strong>Results indicate that hijacked versions of medical journals are published in most fields of the medical domain and typically respect the primary domain of the original journal.</p><p><strong>Conclusion: </strong>The academic world is faced with the third-generation of hijacked journals, and their detection may be more complex than common ones. The usage of artificial intelligence (AI) can be a powerful tool to deal with the phenomenon.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 2","pages":"255-261"},"PeriodicalIF":3.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenogeneic Transplantation Promoted Human Exosome Sequestration in Rat Specific Organs","authors":"Halimeh Mobarak, M. Mahdipour, Arshad Ghaffari-Nasab, R. Rahbarghazi","doi":"10.34172/apb.2024.022","DOIUrl":"https://doi.org/10.34172/apb.2024.022","url":null,"abstract":"Purpose Exosomes (Exos) are introduced as novel cell-free therapeutics with multiple benefits alongside and/or over-cell therapy. Here, we aimed to study the distribution pattern of normal and cancer xenogeneic Exos and possible interspecies reactions in a rat model. Methods Exos were isolated from normal HUVECs and MDA-MB-231 breast cancer cells. Values like mean diameter size and zeta potential distribution were studied using DLS. The morphology of isolated Exos was monitored by SEM images. Using western blotting, protein levels of exosomal tetraspanins were detected. For the in vivo study, Dil-labeled normal and cancer Exos were injected into the tail vein (100 µg exosomal protein/rat) three times at 1-hour intervals. After 24 hours, rats were euthanized and the cellular uptake of Exos was monitored in different organs using immunofluorescence staining (IF). Results The size distribution and mean zeta potential of HUVEC and MDA-MB-231 cells Exos were 80 ± 29.94 and 64.77 ± 25.49 nm, and −7.58 and −11.8 mV, respectively. Western blotting revealed CD9, CD81, and CD63 in normal and cancer Exos. The SEM images exhibited typical nano-sized round-shape Exo particles. IF staining indicated sequestration of administrated Exos in splenic tissue and lungs. The distribution of Exo in kidneys, aorta, and hepatic tissue was less. These features were more evident in the group that received cancer Exos. We found no obvious adverse effects in rats that received normal or cancer Exos. Conclusion Data indicated that both normal and cancerous xenogeneic human Exos can be sequestrated prominently in splenic tissue and lungs. Novel delivery approaches and engineering tools are helpful in the target delivery of administrated Exos to the injured sites","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"75 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138604455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}