Pharmaceutical Development and Technology最新文献

{"title":"Targeted delivery strategy of indocyanine green-mitoxantrone loaded liposomes co-modified with BTP-7 and BR2 for the treatment of glioma.","authors":"Lin Jing, Jingguo Du, Yichao Dong, Lili Li, Zijun Tang, Xu Liu, Yonglong Zhong, Mingqing Yuan","doi":"10.1080/10837450.2024.2448619","DOIUrl":"10.1080/10837450.2024.2448619","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to develop a dual-ligand-modified targeted drug delivery system by integrating photosensitizers and chemotherapeutic drugs to enhance anti-glioma effects. The system is designed to overcome the blood-brain barrier (BBB) that hinders effective drug delivery, increase drug accumulation in glioma cells, and thereby enhance therapeutic efficacy.</p><p><strong>Methods: </strong>Liposomes were prepared using the film dispersion-ammonium sulfate gradient technique, co-loading the photosensitizer indocyanine green (ICG) and the chemotherapeutic drug mitoxantrone (MTO). The conjugation of BTP-7 and BR2 to the liposome surface was achieved using an organic phase reaction method. The stability, dispersibility, particle size, and potential of the modified liposomes were tested. Their ability to penetrate the BBB and accumulate in glioma was evaluated in BBB models and cellular uptake studies. Additionally, the anti-tumor activity of this combination approach was assessed.</p><p><strong>Results: </strong>The resulting liposomes demonstrated significant stability and dispersibility, with an average particle size of 142.3 ± 1.8 nm and a potential of -17.6 mV. BBB model and cellular uptake studies indicated that BTP-7/BR2-ICG/MTO-LP could not only penetrate the BBB but also accumulate in glioma, leading to glioma cell necrosis. The anti-tumor activity evaluation showed that this combination approach exhibited a strong tumor-suppressing effect.</p><p><strong>Conclusion: </strong>The dual-ligand-modified liposomes developed in this study can penetrate the blood-brain barrier and achieve targeted drug delivery in glioma therapy. The combination of BTP-7 and BR2 not only enhances the carrier's penetration ability but also increases intracellular drug accumulation, thereby improving therapeutic efficacy. This novel therapeutic approach, which combines chemotherapy and photothermal response <i>via</i> dual-ligand-modified liposomes delivered to the tumor site, demonstrates the potential to reduce drug-related side effects and improve treatment outcomes.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"90-100"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915393","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":"Intensification of quercetin nanobubble formulation and performance by multi-factor optimization and interaction analysis.","authors":"Hema Kumar A V, Chamakuri Kantlam","doi":"10.1080/10837450.2024.2441182","DOIUrl":"10.1080/10837450.2024.2441182","url":null,"abstract":"<p><p>The natural flavonoid Quercetin (QT) showed a potential for various health benefits, but its pharmaceutical applications are hindered by low solubility, permeability, and limited bioavailability. This research aimed to synthesize, develop and optimize polylactic acid co-glycolic acid (PLGA) nanobubbles using solvent evaporation method as a sustained delivery system for QT, thus improving stability and bioavailability. Through a four-factor, three-level Box Behnken Design, 29 experimental runs were carried out to optimize QT-PLGA nanobubbles. An optimized formulation consisted of 50 mg QT, 250 mg PLGA, and 1.89% <i>w/v</i> PVA. The nanobubbles displayed a particle size of 139.5 ± 6.24 nm, polydispersity index of 0.296 ± 0.19, and zeta potential of -23.0 ± 3.44 mV, with an entrapment efficiency of 59.24 ± 3.08%. Analysis through Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed no drug-polymer interaction, while scanning electron microscopy revealed a uniform spherical nanoparticle. <i>In vitro</i> studies exhibited an excellent drug release, and stability studies showed no significant changes after one month. <i>In vivo</i> studies in rats demonstrated increased <i>C</i>_max (3.03) and <i>AUC</i>_0-t (5.84), indicating an improved sustained release and absorption. These findings underscored a potential of QT-loaded PLGA nanobubbles to enhance the drug kinetics and bioavailability, offering possibilities for targeted drug delivery and improved therapeutic outcomes.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"10-24"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882569","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":"Inhibition of growth and lung metastasis of breast cancer by pH-responsive methotrexate/curcumin-loaded chitosan-stabilized nanoemulsions.","authors":"Mehrnoosh Nikpour, Zahra Karami, Samaneh Rafieenia, Arghavan Adibifar, Shaghayegh Yazdani, Fatemeh Saghatchi Zanjani, Tohid Mortezazadeh, Zahra Abdi, Kobra Rostamizadeh","doi":"10.1080/10837450.2024.2448335","DOIUrl":"10.1080/10837450.2024.2448335","url":null,"abstract":"<p><p>Chemotherapeutic agents are widely used to combat breast cancer. However, due to their non-selective biodistribution, their usage is associated with severe adverse effects on healthy tissues. In this study, a chitosan-stabilized nanoemulsion (CSNE) was prepared for the codelivery of curcumin (CUR) and methotrexate (MTX). The mean diameter and polydispersity index of CUR-MTX-CSNEs were 194.63 ± 6.7 nm and 0.27 ± 0.06, respectively. Modifying the nanoemulsion surface with chitosan decreased the drug release at pH 7.4 compared to pH 5.8. The MTT test demonstrated that CUR-MTX-CSNEs were more successful in reducing the cell viability of 4T1 cells than both bare formulation and free drugs. Moreover, compared to the free drug-treated group, a 2.6 times reduction of the relative tumor volume was witnessed in CUR-MTX-CSNEs-receiving mice. Histopathological studies confirmed a more substantial inhibitory effect on tumor growth and pulmonary metastasis of developed nanostructures than free CUR/MTX. While there was no noticeable toxicity in the vital organs of CUR-MTX-CSNEs-receiving mice, free drugs resulted in severe toxicity in the liver, kidney, lung and spleen. Overall, the pH-dependent drug release, improved anti-tumor activity and reduced organ toxicity suggest that CUR-MTX-CSNE may be promising in breast cancer therapy.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"57-68"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952933","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":"Formation and stabilization mechanism of Ginsenoside Rg3 inclusion complexes based on molecular simulation.","authors":"Shili Pan, Wei Shen, Xuehui Ding, Jingying Li, Jiahui Xu, Jixin Li, Ye Qiu, Wei Xu","doi":"10.1080/10837450.2024.2448618","DOIUrl":"10.1080/10837450.2024.2448618","url":null,"abstract":"<p><p>The formation of inclusion complexes between Ginsenoside Rg3 and cyclodextrins represents a promising strategy to enhance the solubility of G-Rg3. Nevertheless, the molecular mechanisms underlying the interaction between G-Rg3 and cyclodextrins have yet to be fully elucidated. In this study, we employed a combination of molecular simulation and experimental methodologies to identify the most effective solubilizing carriers among G-Rg3, β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and 2,6-dimethyl-β-cyclodextrin (DM-β-CD). The inclusion complexes formed with HP-β-CD demonstrates superior stability and water solubility compared to those formed with β-CD and DM-β-CD. The preparation process for the inclusion complexes of G-Rg3 and HP-β-CD was optimized through an orthogonal testing approach. The optimal conditions were determined to be a mass ratio of G-Rg3 to HP-β-CD of 1:125, an inclusion time of 2 h, and an inclusion temperature of 30 °C. The formation of the inclusion complexes was confirmed using DSC, Fourier Transform Infrared FTIR, and XRD techniques. <i>In vitro</i> solubility tests indicated that the solubility of the G-Rg3 inclusion complexes was 2.9 times greater than that of G-Rg3. Molecular dynamics (MD) simulations provided insights into the mechanisms that stabilize the inclusion complexes and enhance their water solubility. The primary interaction force between G-Rg3 and HP-β-CD was identified as the van der Waals force.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"79-89"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915389","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":"Drug-silica-cellulose ternary matrix for the oral delivery of Cyclosporine A: <i>in vitro</i> and <i>in vivo</i> evaluation.","authors":"Pinal Chaudhari, Vivek M Ghate, Arun K Kodoth, Sumit Birangal, Shaila A Lewis","doi":"10.1080/10837450.2024.2448625","DOIUrl":"10.1080/10837450.2024.2448625","url":null,"abstract":"<p><strong>Purpose: </strong>Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation <i>via</i> molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA.</p><p><strong>Methods: </strong>A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation.</p><p><strong>Results: </strong>The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The <i>in vitro</i> dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC.</p><p><strong>Conclusion: </strong>The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"114-125"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927378","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":"Thermoresponsive biomaterial system of irinotecan and curcumin for the treatment of colorectal cancer: <i>in-vitro</i> and <i>in-vivo</i> investigations.","authors":"Aleena Maryiam, Sibgha Batool, Zakir Ali, Fatima Zahid, Ali H Alamri, Taha Alqahtani, Adel Al Fatease, Ahmed A Lahiq, Muhammad Waseem Khan, Fakhar Ud Din","doi":"10.1080/10837450.2024.2448334","DOIUrl":"10.1080/10837450.2024.2448334","url":null,"abstract":"<p><p>This study aims to develop a thermoresponsive biomaterial system of irinotecan (IRT) and curcumin (CUR) nano-transferosomal gel (IRT-CUR-NTG) for targeting colorectal cancer (CRC). The IRT-CUR-NTs were statistically optimized and loaded into poloxamer-based thermosensitive gel. Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) of the IRT-CUR-NTs were performed, whereas pH, gelation time, gelation temperature, gel and mucoadhesive strength of the IRT-CUR-NTG were investigated. <i>In-vitro</i> release and anticancer analyses were explored using HT29 cells. Additionally, <i>in-vivo</i> pharmacokinetics study was investigated followed by histopathological examination and <i>in-vivo</i> anticancer analysis. The PS, PDI, ZP, %EE of IRT and %EE of CUR were found to be 136.15 nm, 0.143, -15.5 mV, 95.05% and 85.12%, respectively. IRT-CUR-NTs exhibited spherical shape with no chemical interactions among the constituents. Similarly, IRT-CUR-NTG was homogenous gel suitable for rectal administration. IRT-CUR-NTG manifested prolonged release profiles of IRT and CUR. Moreover, a significantly enhanced (4-fold) bioavailability and no toxicity of IRT-CUR-NTG was observed when compared with conventional gel. IRT-CUR-NTs were found to be more effective against HT29 cell lines. <i>In-vivo</i> antitumor analysis demonstrated significantly reduced tumor volume and tumor mass after treatment with IRT-CUT-NTG, indicating improved antitumor effect. It can be concluded that IRT-CUR-NTG is suitable biomaterial system for colorectal cancer.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"37-56"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896415","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":"Thymoquinone loaded lipid nanocapsule dispersion: two methods of preparation, characterization and <i>in vitro</i> evaluations for oral administration.","authors":"Mouna Selmi, Amine Trabelsi, Nolwenn Lautram, David Dallerac, Guillaume Lefebvre, Leila Chekir Ghedira, Emilie Roger","doi":"10.1080/10837450.2024.2448616","DOIUrl":"10.1080/10837450.2024.2448616","url":null,"abstract":"<p><p>This work explores two methods to encapsulate Thymoquinone (TQ) into lipid nanocapsules (LNCs) for oral administration. TQ was added during the phase inversion temperature method (TQ-LNCs-1) or to unload LNCs dispersion (TQ-LNCs-2). LNCs were evaluated for mean diameter, polydispersity index (PDI), ζ-potential, drug loading (DL), drop tensiometer, storage stability, <i>in vitro</i> stability in simulated gastrointestinal fluids (SGIF), and intestinal permeability across Caco-2 cells. TQ-LNCs-1 and TQ-LNCs-2 produced NPs (58.3 ± 3.7 nm and 61.5 ± 3.5 nm, respectively), with a DL of 8.7 ± 0.2 and 7.7 ± 0.6 mg/mL of suspension, respectively. For both, less than 14% of TQ was released in SGIF, and a minor increase in TQ intestinal permeability with LNCs compared to free TQ was observed. TQ-LNCs represented a promising formulation for oral delivery of TQ. Encapsulation of TQ by adding it at LNCs dispersion can be extended for further drugs.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"69-78"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922583","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":"Pharmaceutical excipients in pediatric and geriatric drug formulations: safety, efficacy, and regulatory perspectives.","authors":"Tansel Comoglu, Emine Dilek Ozyilmaz","doi":"10.1080/10837450.2024.2441181","DOIUrl":"10.1080/10837450.2024.2441181","url":null,"abstract":"<p><p>Pharmaceutical excipients are indispensable components of drug formulations, playing critical roles in enhancing stability, improving bioavailability, and ensuring patient compliance. In pediatric and geriatric populations, the selection of these excipients becomes even more crucial due to their unique physiological and pharmacokinetic profiles, as well as age-specific formulation requirements. This review examines the functions, safety considerations, and potential adverse effects of excipients in these vulnerable groups. It addresses the challenges of drug formulation for neonates, infants, and elderly patients, including immature enzyme systems, polypharmacy, and swallowing difficulties. The impact of excipient-excipient and excipient-active pharmaceutical ingredient (API) interactions on drug stability, efficacy, and safety is also highlighted. For instance, the effects of polyethylene glycol (PEG) in patients with impaired renal function and destabilizing interactions between surfactants and protein-based APIs are analyzed. Additionally, current guidelines and safety requirements from regulatory bodies such as the FDA, EMA, and ICH are reviewed. This paper emphasizes the importance of carefully selecting excipients that balance functionality and safety to ensure therapeutic efficacy while minimizing risks for pediatric and geriatric patients. Future directions in excipient development and formulation strategies are also discussed to improve treatment outcomes for these populations.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-9"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807677","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":"Indomethacin-encapsulated PLGA nanoparticles improve therapeutic efficacy by increasing apoptosis and reducing motility in glioblastoma cells.","authors":"Ferhat Bostancı, Aslıhan Şengelen, Yunus Aksüt, Eren Yıldırım, İrem Öğütcü, Oğuz Yücel, Serkan Emik, Gülten Gürdağ, Murat Pekmez","doi":"10.1080/10837450.2024.2448333","DOIUrl":"10.1080/10837450.2024.2448333","url":null,"abstract":"<p><p>Glioblastoma, with a low survival rate, is an aggressive and difficult-to-treat lethal type of brain cancer. Indomethacin (IND), a non-steroidal anti-inflammatory drug, has antitumoral activity in many cancers, including gliomas. However, its poor aqueous solubility is a critical issue. Nanomaterials are crucial tools for overcoming solubility problems and facilitating drug delivery. Herein, a polymeric nanoparticle system, poly(lactic-co-glycolic acid) (PLGA) was used to encapsulate IND. Although PLGA is an FDA-approved copolymer for drug delivery, no trials with IND-loaded PLGA-NPs have been conducted to treat brain tumors. Encapsulation success was revealed by DLS, zeta potential, TEM, and FTIR analysis; IND/PLGA-NPs had nanoscale particle size (160.6 nm), narrow size distribution (0.230, PDI), and good stability (-23.9 mV). Fluorescence imaging showed that PLGA-NPs can penetrate U-87MG cells. Short-term/one-hour treatment with bound-IND increased the free-IND effect in gliomas by ⁓10 times/48h and 12.39 times/72h. Even against long-term exposure to IND, IND/PLGA-NP treatment revealed a highly marked result; the IC₅₀ value of bound-IND (treatment-time:1h, analysis at 48h) was ∼200µM, IC₅₀ value of free-IND (treatment-time:48h) was ∼390µM. Furthermore, IND/PLGA-NPs' anticancer activity (100 µM of IND/1h, analysis at 48h) was also supported by induced apoptosis and reduced migration/colony formation in glioma cells. All evidence suggests that IND/PLGA-NPs may be a potentially promising agent for treating gliomas.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"25-36"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922527","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":"Preparation and characterization of poly(ethylene glycol)-<i>b</i>-poly(<i>tert</i>-butyl methacrylate) micelles as potential nanocarriers for donepezil.","authors":"Gizem İğdeli, Laura Fritzen, Claus U Pietrzik, Binnur Aydogan Temel","doi":"10.1080/10837450.2024.2423833","DOIUrl":"10.1080/10837450.2024.2423833","url":null,"abstract":"<p><p>Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer's disease drug, to enhance its transport across the blood-brain barrier (BBB). Poly(ethylene glycol)-<i>b</i>-poly(<i>tert</i>-butyl methacrylate) amphiphilic block copolymers were synthesized <i>via</i> reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated <i>via</i> colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an <i>in vitro</i> BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer's treatment by enhancing donepezil's delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer's therapy.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1111-1120"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546707","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}