AAPS PharmSciTech最新文献

{"title":"Evaluation of Physicochemical, Microstructure Parameters (Q3) and Performance Attributes of Commercial Ketoprofen Gels","authors":"Şeyma İşkin,&nbsp;Emine Kahraman,&nbsp;Sevgi Güngör","doi":"10.1208/s12249-025-03044-4","DOIUrl":"10.1208/s12249-025-03044-4","url":null,"abstract":"<div><p><i>In vitro</i> methods for quality and equivalence assessment of semi-solid products applied to the skin have increasingly garnered attention because <i>in vivo</i> bioequivalence studies is high cost, complexity, and time-consuming. Regulatory authorities established draft guidelines that outline a modular framework demanding qualitative, quantitative, microstructure and product performance equivalence to support generic products. In line with these guidelines, our study aimed to evaluate the relationship between microstructure and performance attributes in both originator and generic semi-solid products applied to the skin. In this context, reference and three generics of ketoprofen gel were selected as models for semi-solid formulations. Microstructure of all products was assessed regarding pH, specific gravity, drying rate, formulation rheology and potential drug polymorphism. Additionally, performance attributes of products were evaluated using <i>in vitro</i> release testing and <i>in vitro</i> permeation testing. Polymorphism and drying rate data showed no significant difference in microstructure of ketoprofen gels. All tested products exhibited <i>pseudo-plastic</i> flow behavior with <i>thixotropic</i> characteristic. However, differences in pH, specific gravity and viscosity values at low shear stress were observed between reference product and generic products, according to EMA guidance. Although IVRT outcomes did not entirely align with Q3 attributes, IVRT results for reference product <i>versus</i> Generic Product-I and Generic Product-II met the acceptance limits according to FDA guidance, which differs from EMA's assessment. Furthermore, <i>in vitro</i> release rate results were consistent with IVPT data. Consequently, it can be concluded that microstructure of semi-solid products applied to the skin may not consistently correlate with performance attributes due to various alternations influenced by manufacturing process parameters and/or formulation components.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03044-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Interpolyelectrolyte Complexes Based on Eudragit® RL and Oppositely Charged Eudragit® Polyanions as a Novel Matrix System for Colon-specific Drug Delivery","authors":"Rouslan I. Moustafine,&nbsp;Natalia N. Porfiryeva,&nbsp;Shamil F. Nasibullin,&nbsp;Alexander Y. Sitenkov,&nbsp;Aleksandra V. Sitenkova,&nbsp;Venera R. Timergalieva,&nbsp;Vera A. Kemenova","doi":"10.1208/s12249-024-03025-z","DOIUrl":"10.1208/s12249-024-03025-z","url":null,"abstract":"<div><p>The design of new interpolyelectrolyte complexes (IPEC) between Eudragit^® polycation (type RL) and oppositely charged Eudragit^® polyanions (types L100-55, L100, S100, FS) was investigated. The formation and chemical composition of novel IPECs between countercharged Eudragit^® copolymers was established by gravimetric and elemental analysis. The structure and solid state properties of the synthesized IPEC were investigated comparatively to correspondent physical mixtures pairs of copolymers in similar molar ratio, using Fourier transform infrared (FTIR) spectroscopy and modulated temperature differential scanning calorimetry (mDSC). The binding ratio of a unit molecule of RL with polyanions was found to range between 1.73:1 and 4.19:1 while increasing the percentages of carboxylic groups in their structures from 10% (FS) to 50% (L100-55). As a result of electrostatic interaction between the copolymer chains, the glass transition temperature of the IPEC changed significantly. Considerable pH-sensitive swelling in acidic and neutral media was observed for different type of IPECs. Through evaluation of diffusion-transportation properties of the IPECs, basic mechanisms controlling the delivery of indomethacin were obtained. The results of swelling and release of the model drug from the polycomplex matrices confirm that they have potential to be used in colon-specific drug delivery.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Based Prediction of Drug Solubility in Lipidic Environments: The Sol_ME Tool for Optimizing Lipid-Based Formulations with a Preliminary Apalutamide Case Study","authors":"Swayamprakash Patel,&nbsp;Ami Kalasariya,&nbsp;Jagruti Desai,&nbsp;Mehul Patel,&nbsp;Ashish Patel,&nbsp;Umang Shah","doi":"10.1208/s12249-025-03051-5","DOIUrl":"10.1208/s12249-025-03051-5","url":null,"abstract":"<p>Lipid-based formulations are essential for enhancing drug solubility and bioavailability, yet selecting optimal lipid excipients for specific drugs remains challenging. This study introduces Sol_ME, a machine learning-based model designed to predict drug solubility in lipidic environments, thereby streamlining the formulation process. The Sol_ME model uses PubChem® fingerprints, focusing on solubility correlations with lipid excipients, minimizing reliance on traditional parameters like LogP and molecular weight. The model was trained on a dataset of 1,379 drug-solvent entries and applied to the formulation of Apalutamide, a BCS Class II drug. Experimental validation was performed with 35 drug-solvent combinations to assess the accuracy of predicted solubilities. Sol_ME achieved a high predictive accuracy with a correlation coefficient of 0.998. The model successfully identified Cinnamon oil as the optimal excipient for Apalutamide, further refining the formulation with Vanillin. This reduced formulation volume by 75%, enabling the development of a single-unit 240 mg soft gelatin capsule. Experimental validation showed 80% alignment between predicted and actual solubilities. The Sol_ME model demonstrates significant potential to optimize lipid-based drug formulation, offering a data-driven approach that enhances efficiency. The success of Apalutamide formulation highlights its practical utility. Future work will expand the dataset and extend the model to solid lipid systems, broadening its application in drug delivery technologies.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal Delivery of Paclitaxel-Loaded Ligand Conjugated Polymeric Nanoparticles for Targeted Brain Delivery","authors":"Vishawambhar Deshmukh,&nbsp;Mahaveer Narwade,&nbsp;Kavita Rai Gajbhiye","doi":"10.1208/s12249-025-03046-2","DOIUrl":"10.1208/s12249-025-03046-2","url":null,"abstract":"<div><p>Compared to the conventional blood–brain barrier crossing over, nose-to-brain delivery provides a potentially effective substitution, particularly when large molecules of drugs need to be delivered. The majority of macromolecules degrade quickly in a physiological environment. Therefore, drug molecules can be protected against early breakdown by using nanocarrier systems. Targeting nanocarrier system with ligand potential of enhancing bioavailability due to tailored binding affinity to targeting site. In the current study, we prepared paclitaxel (PTX) loaded ascorbic acid (AA) conjugated polycaprolactone (PCL) nanoparticles (NPs) for intranasal administration. Polymeric nanoparticles (PNPs) were prepared using the solvent evaporation method, which was further analyzed for particle size, polydispersity index (PDI), surface charge, encapsulation-efficiency (EE), drug loading (DL), surface morphology, <i>in-vitro</i> drug release, and <i>in-vivo</i> pharmacokinetic evaluation. Results showed the optimized PTX-PNPs showed particle size 114.7 ± 2.96 nm, zeta potential -27.6 ± 1.63 mV, with entrapment efficiency 97.3 ± 0.41%, and drug loading 35.3 ± 0.38%. <i>In-vitro</i> PTX release showed a biphasic release pattern, primary burst release followed by sustained release was observed. An <i>in-vivo</i> pharmacokinetic study showed a 5.6-fold increase in the PTX concentration reaching to the brain. Histopathological results of the nasal mucosa showed minimal alteration after 72 h of administering surface-modified paclitaxel loaded polymeric nanoparticles (AA-PTX-PNPs). Thus, this study highlighted the suitability of a AA-PTX-PNPs as a promising strategy for intranasal administration therapy for various brain disorders.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Stabilized and Highly Soluble Bezafibrate-Gliclazide Co-Amorphous Binary System","authors":"Jorge Cruz-Angeles,&nbsp;Luz María Martínez,&nbsp;Alice M López López,&nbsp;Paulina Cabada-Aguirre,&nbsp;Marcelo Videa,&nbsp;Alejandra Flores","doi":"10.1208/s12249-025-03045-3","DOIUrl":"10.1208/s12249-025-03045-3","url":null,"abstract":"<div><p>Metabolic syndrome (MS) has a high prevalence, with an estimated one-quarter of the world population affected by this pathological condition. Among the diseases of this syndrome are dysregulation of lipids, hypertension, and insulin resistance. Unfortunately, available drugs in the market used for treating MS, as almost 75% of all drugs, are highly insoluble, presenting a significant demand for strategies to increase their solubility. Taking advantage of the fact that drugs in the amorphous state can provide a solubility enhancement, a new drug-drug co-amorphous (CoA) formulation to potentially simultaneously treat two or more MS conditions was explored, combining the co-formers Bezafibrate (BZT) a lipid-regulating drug, and Gliclazide (GZD) a hypoglycemic agent. A phase diagram was constructed to characterize the binary system's thermal properties, including glass transition temperatures of all compositions studied. The formulations were characterized by FTIR; redshifts of IR bands from 1547 to 1538 cm^–1 and 1717 to 1609 cm^–1 were observed due to the formation of intermolecular interactions, such as hydrogen bonds. The co-amorphous binary systems lead to an increase in the solubility of both BZT and GZD; specifically, for the composition x_BZT = 0.5, the increase was 2.1× for BZT and 1.5 times for GZD while for x_BZT = 0.7 an increase of 4× of BZT was achieved. The structural stability of the samples was verified by XRD and DSC, showing long-term stability retention of the amorphous state for more than eight years. The enhanced solubility and stability of the co-amorphous systems make them potential formulations for regulating lipids and lowering glycemia.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing Soluplus®-Based Microparticle Amorphous Solid Dispersions with High Drug Loading for Enhanced Celecoxib Dissolution via Electrospraying","authors":"Fan Fan,&nbsp;Feng Zhou,&nbsp;Jiayu Zhang,&nbsp;Junhui Yang,&nbsp;Kai Zhuang,&nbsp;Yudong Shan,&nbsp;Lei Jiang,&nbsp;Jiantao Zhang","doi":"10.1208/s12249-025-03041-7","DOIUrl":"10.1208/s12249-025-03041-7","url":null,"abstract":"<div><p>Amorphous solid dispersion (ASD) is one of the most studied strategies for improving the dissolution performance of poorly water-soluble drugs, but ASDs often have low drug loadings, thereby necessitating larger dosage sizes. This study intended to create Soluplus® (SOL)-based microparticle ASDs with high drug loading (up to 60 w/w%) and long-term stability (at least 16 months) using electrospraying to enhance the dissolution of poorly water-soluble celecoxib (CEL). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed that the electrosprayed SOL-CEL microparticles were amorphous, and Fourier transform infrared spectroscopy (FTIR) data indicated the presence of hydrogen bonding between SOL and CEL in the microparticles, which helped stabilize the ASDs. <i>In vitro</i> dissolution studies demonstrated that these ASDs improved the CEL dissolution rate by up to 8.2-fold compared to the crystalline form. Electrospraying presents a promising alternative to conventional methods like hot-melt extrusion (HME) and spraying drying (SD) for the production of ASDs, providing simplicity, high drug loading capability and long-term stability, thus catering to a variety of poorly water-soluble drugs.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosimilars: A Critical Review of Development, Regulatory Landscape, and Clinical Implications","authors":"Ankit Monga,&nbsp; Gagan,&nbsp;Pragya Jamwal,&nbsp;Sumit Sharma,&nbsp;Amanpreet Kaur","doi":"10.1208/s12249-025-03038-2","DOIUrl":"10.1208/s12249-025-03038-2","url":null,"abstract":"<div><p>The biopharmaceutical industry has witnessed significant growth in the development and approval of biosimilars. These biosimilars aim to provide cost-effective alternatives to expensive originator biosimilars, alleviating financial pressures within healthcare. The manufacturing of biosimilars is a highly complex process that involves several stages, each of which must meet strict regulatory standards to ensure that the final product is highly similar to the reference biologic. To gain regulatory approval, biosimilars must undergo rigorous analytical characterization including <i>in vitro</i> assays, bioanalytical evaluations, and clinical similarity studies like pharmacokinetic (PK), pharmacodynamic (PD) assessments-to demonstrate safety, efficacy, quality comparability with reference products. Leading regulatory agencies such as the European Medicines Agency (EMA), the World Health Organization (WHO), and the United States Food and Drug Administration (US FDA) have established stringent guidelines for biosimilar evaluation and post-marketing surveillance. Despite this regulatory clarity, challenges around interchangeability, market exclusivity, and patent protection often delay market access and limit adoption, particularly in regions where automatic substitution is restricted. Case studies of biosimilars such as rituximab, adalimumab, filgrastim, and trastuzab reveal both advancements and ongoing hurdles in achieving broader market integration. The introduction of biosimilars has shown potential to reduce healthcare costs; for example, a recent analysis indicates a 20–30% cost reduction in the U.S. due to biosimilar adoption. As the biosimilar market expands, collaborative efforts among regulatory bodies, industry stakeholders, and healthcare providers are essential to enhance access to biologic therapies. This collaboration is poised to improve patient outcomes and catalyse transformative change in global healthcare systems.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valsartan Loaded Solid Self-Nanoemulsifying Delivery System to Enhance Oral Absorption and Bioavailability","authors":"Lusi Chen,&nbsp;Xin Zhang,&nbsp;Jiayu Xie,&nbsp;Tao Xiao,&nbsp;Huiying Zhong,&nbsp;Haibing He,&nbsp;Guoqing Zhang,&nbsp;Hongfei Liu","doi":"10.1208/s12249-024-03032-0","DOIUrl":"10.1208/s12249-024-03032-0","url":null,"abstract":"<div><p>Valsartan (VST) is an angiotensin II receptor antagonist with low oral bioavailability. The present study developed a solid self-nanoemulsifying drug delivery system (S-SNEDDS) to enhance the oral absorption and bioavailability of VST. VST-loaded liquid SNEDDS (VST@L-SNEDDS) was prepared by investigating the solubility of VST and constructing the pseudo-ternary phase diagrams. The formulation of VST@S-SNEDDS was obtained by adsorbing VST@L-SNEDDS onto a solid carrier. <i>In vitro</i> studies including drug dissolution, stability, cytotoxicity, and Caco-2 uptake of VST@S-SNEDDS were assessed. An <i>in vivo</i> pharmacokinetic study of VST@S-SNEDDS was employed to evaluate the oral bioavailability of VST. VST@L-SNEDDS, with an average particle size of 19.90 nm and zeta potential of -20.57 mV, consisted of 12.37% VST (drug loading), 21.91% ethyl oleate, 45.50% RH 40, and 20.22% Transcutol HP. VST@S-SNEDDS was prepared using Neusilin® UFL2 as a solid adsorbent, which contained VST@L-SNEDDS at 2.28 ± 0.15 g/g. The <i>in vitro</i> release study demonstrated that VST@S-SNEDDS exhibited rapid release characteristic without affecting by the pH of the media, and dissolution rates exceeded 90% within 60 min in different media. The long-term stability of VST@S-SNEDDS was better than that of VST@L-SNEDDS. These two formulations increased the Caco-2 uptake significantly. The area under the drug concentration–time curve (AUC_0-24h) and peak drug concentration in plasma (C_max) of VST@S-SNEDDS increased by 2.28-fold and 4.86-fold compared to raw VST, respectively. The proposed VST@S-SNEDDS represents a novel approach to enhance the oral absorption and bioavailability of VST, providing a promising avenue for hypertension treatment.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Process Considerations for Preparation of Modified Release Ivermectin and Praziquantel Tablets by Wet Granulation","authors":"R. Gary Hollenbeck,&nbsp;Raafat Fahmy,&nbsp;Marilyn N. Martinez,&nbsp;Ahmed Ibrahim,&nbsp;Stephen W. Hoag","doi":"10.1208/s12249-024-03030-2","DOIUrl":"10.1208/s12249-024-03030-2","url":null,"abstract":"<div><p>Dosage forms containing Ivermectin (IVER) and Praziquantel (PRAZ) are important combination drug products in animal health. Understanding the relationship between products with differing <i>in vitro</i> release characteristics and bioequivalence could facilitate generics. The goal of this study was to create granulations for each active ingredient, with similar release mechanisms, but substantially different <i>in vitro</i> release rates, and then compressing these granulations into tablets with differing release rates. Four granulation formulations were created: fast and modified release for PRAZ and IVER, respectively. The manufacturing process used high shear wet granulation and fluid bed drying, milling and sieving. Solid components, including the granulating agent, were blended in a high shear granulator and then water or a hydroalcoholic solution was added to activate the binder and initiate granule formation. Drying in a fluid bed with inlet air temperature set for 70°C and inlet air volume adjusted as required to maintain fluidization. Milling was performed in a cone mill and classification of final product was done using a vibratory sieve shaker with 18, 20, 40, and 60 mesh sieves. Formulations and processing approaches were successfully developed to produce a collection of PRAZ and IVER granules with differing particle size distributions and <i>in vitro</i> release characteristics. Differences in drug content in the classified granulations were observed and attributed to the low surface energy of PRAZ and the different approaches used to incorporate the active ingredients. The granulations were compressed via compaction simulator and the results show the monolithic tablets had four different release profiles.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Plasma-Derived Exosomes: A Promising Carrier System for the Delivery of Hydroxyurea to Combat Breast Cancer","authors":"Wajeeha Khalid,&nbsp;Afeefa Aslam,&nbsp;Nadeem Ahmed,&nbsp;Muhammad Sarfraz,&nbsp;Jawad Akbar Khan,&nbsp;Sabeeh Mohsin,&nbsp;Muhammad Shahid Riaz Rajoka,&nbsp;Imran Nazir,&nbsp;Muhammad Imran Amirzada","doi":"10.1208/s12249-024-03028-w","DOIUrl":"10.1208/s12249-024-03028-w","url":null,"abstract":"<div><p>The aim of the present study was to investigate the potential of human plasma derived exosomes for the delivery of hydroxyurea to enhance its therapeutic efficacy in breast cancer. Plasma derived exosomes were isolated using differential centrifugation along with ultrafiltration method. Hydroxyurea was encapsulated in exosomes using a freeze–thaw method. The exosomes and Exo-HU were characterized for their size distribution, drug entrapment efficiency, <i>in-vitro</i> drug release profile, morphological analysis and cytotoxic effects on MCF-7 cell line. The results showed a mean size of 178.8 nm and a zeta potential of -18.3 mV, indicating good stability and 70% encapsulation effectiveness for HU. Exo-HU produced sustained drug release action with a considerable percentage released within 72 h. The morphological analysis indicated that the plasma derived exosomes were spherical, and cup shaped. In cytotoxicity studies on MCF-7 cells, Exo-HU has reduced cell viability compared to HU and blank exosomes. Findings of this study showed that human plasma-derived exosomes have been considered as effective delivery vehicle for hydroxyurea, potentially improving breast cancer treatment outcomes.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}