Ahmad Saleh Malkawi, Collins Ovenseri Airemwen, Azhar Malkawi
{"title":"多种模型药物离子配合物在优化的表面活性剂和助溶剂胶束基础上的混合胶束配方:体外给药效率分析","authors":"Ahmad Saleh Malkawi, Collins Ovenseri Airemwen, Azhar Malkawi","doi":"10.1007/s12247-025-10041-4","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>In this study, micellar complexes of various model drugs were developed and investigated for drug delivery efficiency.</p><h3>Method</h3><p>Ponceau 4R, captopril, and fluorescein were chosen as model drugs to form ionic complexes with three Eudragit-based polymers (Eudragit RL, RS, and E). The formed model drug complexes were Eudragit RL-ponceau 4R (RLP), Eudragit RS-ponceau 4R (RSP), Eudragit RS-captopril (RSC), Eudragit E-captopril (EC), and Eudragit RS-fluorescein (RSF). RLP, RSP, RSC, EC, and RSF were incorporated into a micellar base composed of 40% Kolliphor RH 40, 20% Kolliphor EL, 15% Capmul MCM, and 25% dipropylene glycol to form MRLP, MRSP, MRSC, MEC, and MRSF micellar complexes, respectively. Micellar complexes were diluted in physiological buffer media (pH 7.4) and characterized regarding the size, polydispersity index (PDI), zeta potential, critical micelle concentration (CMC), and safety on Caco-2 cells. Micellar complex efficiency in model drug delivery was investigated through a drug release study, cellular uptake, and confocal microscopy.</p><h3>Results</h3><p>Micellar complexes preserved a stabilized size (14.38–91.38 nm) with a PDI ≤ 0.3 and exhibited a zeta potential in the range of + 2.21 mV to + 12.23 mV. CMC of all micellar formulations was in the range of 130–230 µg/mL. At 0.5:100, 1:100, 2:100, and 3:100 dilutions, micellar complexes maintained a considerable safety limit, shown as 85–100% cell viability over Caco-2 cells. All micellar complexes were compatible for a sustained drug release with an average of 94.85 ± 1.42% model drug release within 4–6 h. The release pattern of model drugs from the micellar complexes followed First-order kinetics. Comparatively, cellular uptake of model drugs from the micellar complexes was significantly higher as compared to the control of free model drug solutions (p ≤ 0.001). MRLP and MRSP, MRSC and MEC, and MRSF showed 5.7- to 9.4-fold, 2.9- to 4.4-fold, and 4.2-fold higher model drug cellular uptake than ponceau 4R, captopril, and fluorescein as free model drug solutions, respectively. Confocal microscopic imaging showed a remarkable fluorescent intensity as an indication of fluorescein cellular uptake from MRSF.</p><h3>Conclusion</h3><p>The studied micellar complexes provided proof of an efficient drug delivery vehicle by showing a sustained optimum drug release and a significantly enhanced model drug cellular uptake while maintaining adequate biocompatibility.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 4","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Formulation of Mixed Micelles of Various Model Drug Ionic Complexes in an Optimized Micellar Base Composed of Surfactants and Cosolvent Mixture: In Vitro Analysis of Drug Delivery Efficiency\",\"authors\":\"Ahmad Saleh Malkawi, Collins Ovenseri Airemwen, Azhar Malkawi\",\"doi\":\"10.1007/s12247-025-10041-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>In this study, micellar complexes of various model drugs were developed and investigated for drug delivery efficiency.</p><h3>Method</h3><p>Ponceau 4R, captopril, and fluorescein were chosen as model drugs to form ionic complexes with three Eudragit-based polymers (Eudragit RL, RS, and E). The formed model drug complexes were Eudragit RL-ponceau 4R (RLP), Eudragit RS-ponceau 4R (RSP), Eudragit RS-captopril (RSC), Eudragit E-captopril (EC), and Eudragit RS-fluorescein (RSF). RLP, RSP, RSC, EC, and RSF were incorporated into a micellar base composed of 40% Kolliphor RH 40, 20% Kolliphor EL, 15% Capmul MCM, and 25% dipropylene glycol to form MRLP, MRSP, MRSC, MEC, and MRSF micellar complexes, respectively. Micellar complexes were diluted in physiological buffer media (pH 7.4) and characterized regarding the size, polydispersity index (PDI), zeta potential, critical micelle concentration (CMC), and safety on Caco-2 cells. Micellar complex efficiency in model drug delivery was investigated through a drug release study, cellular uptake, and confocal microscopy.</p><h3>Results</h3><p>Micellar complexes preserved a stabilized size (14.38–91.38 nm) with a PDI ≤ 0.3 and exhibited a zeta potential in the range of + 2.21 mV to + 12.23 mV. CMC of all micellar formulations was in the range of 130–230 µg/mL. At 0.5:100, 1:100, 2:100, and 3:100 dilutions, micellar complexes maintained a considerable safety limit, shown as 85–100% cell viability over Caco-2 cells. All micellar complexes were compatible for a sustained drug release with an average of 94.85 ± 1.42% model drug release within 4–6 h. The release pattern of model drugs from the micellar complexes followed First-order kinetics. Comparatively, cellular uptake of model drugs from the micellar complexes was significantly higher as compared to the control of free model drug solutions (p ≤ 0.001). MRLP and MRSP, MRSC and MEC, and MRSF showed 5.7- to 9.4-fold, 2.9- to 4.4-fold, and 4.2-fold higher model drug cellular uptake than ponceau 4R, captopril, and fluorescein as free model drug solutions, respectively. Confocal microscopic imaging showed a remarkable fluorescent intensity as an indication of fluorescein cellular uptake from MRSF.</p><h3>Conclusion</h3><p>The studied micellar complexes provided proof of an efficient drug delivery vehicle by showing a sustained optimum drug release and a significantly enhanced model drug cellular uptake while maintaining adequate biocompatibility.</p><h3>Graphical Abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":656,\"journal\":{\"name\":\"Journal of Pharmaceutical Innovation\",\"volume\":\"20 4\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pharmaceutical Innovation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12247-025-10041-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmaceutical Innovation","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12247-025-10041-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Formulation of Mixed Micelles of Various Model Drug Ionic Complexes in an Optimized Micellar Base Composed of Surfactants and Cosolvent Mixture: In Vitro Analysis of Drug Delivery Efficiency
Objective
In this study, micellar complexes of various model drugs were developed and investigated for drug delivery efficiency.
Method
Ponceau 4R, captopril, and fluorescein were chosen as model drugs to form ionic complexes with three Eudragit-based polymers (Eudragit RL, RS, and E). The formed model drug complexes were Eudragit RL-ponceau 4R (RLP), Eudragit RS-ponceau 4R (RSP), Eudragit RS-captopril (RSC), Eudragit E-captopril (EC), and Eudragit RS-fluorescein (RSF). RLP, RSP, RSC, EC, and RSF were incorporated into a micellar base composed of 40% Kolliphor RH 40, 20% Kolliphor EL, 15% Capmul MCM, and 25% dipropylene glycol to form MRLP, MRSP, MRSC, MEC, and MRSF micellar complexes, respectively. Micellar complexes were diluted in physiological buffer media (pH 7.4) and characterized regarding the size, polydispersity index (PDI), zeta potential, critical micelle concentration (CMC), and safety on Caco-2 cells. Micellar complex efficiency in model drug delivery was investigated through a drug release study, cellular uptake, and confocal microscopy.
Results
Micellar complexes preserved a stabilized size (14.38–91.38 nm) with a PDI ≤ 0.3 and exhibited a zeta potential in the range of + 2.21 mV to + 12.23 mV. CMC of all micellar formulations was in the range of 130–230 µg/mL. At 0.5:100, 1:100, 2:100, and 3:100 dilutions, micellar complexes maintained a considerable safety limit, shown as 85–100% cell viability over Caco-2 cells. All micellar complexes were compatible for a sustained drug release with an average of 94.85 ± 1.42% model drug release within 4–6 h. The release pattern of model drugs from the micellar complexes followed First-order kinetics. Comparatively, cellular uptake of model drugs from the micellar complexes was significantly higher as compared to the control of free model drug solutions (p ≤ 0.001). MRLP and MRSP, MRSC and MEC, and MRSF showed 5.7- to 9.4-fold, 2.9- to 4.4-fold, and 4.2-fold higher model drug cellular uptake than ponceau 4R, captopril, and fluorescein as free model drug solutions, respectively. Confocal microscopic imaging showed a remarkable fluorescent intensity as an indication of fluorescein cellular uptake from MRSF.
Conclusion
The studied micellar complexes provided proof of an efficient drug delivery vehicle by showing a sustained optimum drug release and a significantly enhanced model drug cellular uptake while maintaining adequate biocompatibility.
期刊介绍:
The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories:
Materials science,
Product design,
Process design, optimization, automation and control,
Facilities; Information management,
Regulatory policy and strategy,
Supply chain developments ,
Education and professional development,
Journal of Pharmaceutical Innovation publishes four issues a year.