Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer
Yi-Pin Chen,1,2 Chiao-Fan Chiu,3,4 Chien-Neng Wang,1 Chu-Chi Lin,1 Chia-Rui Shen,5– 7 Yi-Chen Yao,8 Yi-Hua Kuo,8 Shih-Jung Liu8,9 1Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, 20401, Taiwan; 2School of Traditional Chinese Medicine, College of Medicine, Chan...
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Dove Medical Press
2025-01-01
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| author | Chen YP Chiu CF Wang CN Lin CC Shen CR Yao YC Kuo YH Liu SJ |
| author_facet | Chen YP Chiu CF Wang CN Lin CC Shen CR Yao YC Kuo YH Liu SJ |
| author_sort | Chen YP |
| collection | DOAJ |
| description | Yi-Pin Chen,1,2 Chiao-Fan Chiu,3,4 Chien-Neng Wang,1 Chu-Chi Lin,1 Chia-Rui Shen,5– 7 Yi-Chen Yao,8 Yi-Hua Kuo,8 Shih-Jung Liu8,9 1Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, 20401, Taiwan; 2School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pediatrics, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; 4Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; 5Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, 33302, Taiwan; 6Department of Ophthalmology, Lin-Kou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 7R&D Center of Biochemical Engineering Technology, Department of Chemical Engineering, Ming Chi University of Technology, New Taipei, Taiwan; 8Department of Mechanical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan; 9Bone and Joint Research Center, Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Taoyuan, 33305, TaiwanCorrespondence: Shih-Jung Liu, Department of Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, 33302, Taiwan, Tel +886-3-2118166, Fax +886-3-2118558, Email shihjung@mail.cgu.edu.twBackground: In clinical practice, imiquimod is used to treat Human Papillomavirus (HPV)-related lesions, such as condyloma and Cervical Intraepithelial Neoplasia (CIN). Metronidazole is the most commonly prescribed antibiotic for bacterial vaginosis. The study developed biodegradable imiquimod- and metronidazole-loaded nanofibrous mats and assessed their effectiveness for the topical treatment of cervical cancer, a type of HPV-related lesion.Methods: Nanofibers of two distinct poly[(d,l)-lactide-co-glycolide] (PLGA)-to-drug ratios (6:1 and 4:1) were manufactured through the electrospinning technology. The in vitro release behavior of imiquimod and metronidazole was evaluated via an elution method, while the in vivo discharge behavior was evaluated on a mice model. Additionally, a model of cervical cancer was established using C57BL/6J mice, and it was utilized to evaluate the efficacy of drug-eluting nanofibers through in vivo testing. Mice afflicted with cervical cancer were separated into three distinct groups for the study: The mice in Group A served as the control and received no treatment. Group B received treatment with pure PLGA nanofibers (no drugs loaded), whereas Group C received treatment with nanofibers loaded with imiquimod and metronidazole. Post implantation, the variations in tumor sizes of rats receiving the implantation of drug-eluting nanofibers were monitored.Results: The experimental data show that drug-eluting nanofibers could discharge in vitro high concentrations of imiquimod and metronidazole for exceeding 30 days. In vivo, each membrane consistently released elevated concentrations of imiquimod/metronidazole at the intended site in mice over a four-week period, with minimal systemic drug concentration detected in the bloodstream. The mice treated with drug-loaded nanofibers displayed noticeably reduced tumor volumes compared to both the control group and the group treated with pristine nanofibers. Histological examination revealed the absence of any discernible tissue inflammation.Conclusion: Biodegradable nanofibers with a sustainable release of imiquimod and metronidazole demonstrated their effectiveness and lasting impact of treating mice with cervical cancer.Keywords: cervical cancer, degradable nanofibers, imiquimod, metronidazole, extended drug release |
| format | Article |
| id | doaj-art-9af2207142754e83b6b26fd98bc38567 |
| institution | Kabale University |
| issn | 1178-2013 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Dove Medical Press |
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| series | International Journal of Nanomedicine |
| spelling | doaj-art-9af2207142754e83b6b26fd98bc385672025-01-21T16:58:06ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-01-01Volume 2095196699435Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical CancerChen YPChiu CFWang CNLin CCShen CRYao YCKuo YHLiu SJYi-Pin Chen,1,2 Chiao-Fan Chiu,3,4 Chien-Neng Wang,1 Chu-Chi Lin,1 Chia-Rui Shen,5– 7 Yi-Chen Yao,8 Yi-Hua Kuo,8 Shih-Jung Liu8,9 1Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, 20401, Taiwan; 2School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pediatrics, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan; 4Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; 5Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, 33302, Taiwan; 6Department of Ophthalmology, Lin-Kou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 7R&D Center of Biochemical Engineering Technology, Department of Chemical Engineering, Ming Chi University of Technology, New Taipei, Taiwan; 8Department of Mechanical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan; 9Bone and Joint Research Center, Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Taoyuan, 33305, TaiwanCorrespondence: Shih-Jung Liu, Department of Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, 33302, Taiwan, Tel +886-3-2118166, Fax +886-3-2118558, Email shihjung@mail.cgu.edu.twBackground: In clinical practice, imiquimod is used to treat Human Papillomavirus (HPV)-related lesions, such as condyloma and Cervical Intraepithelial Neoplasia (CIN). Metronidazole is the most commonly prescribed antibiotic for bacterial vaginosis. The study developed biodegradable imiquimod- and metronidazole-loaded nanofibrous mats and assessed their effectiveness for the topical treatment of cervical cancer, a type of HPV-related lesion.Methods: Nanofibers of two distinct poly[(d,l)-lactide-co-glycolide] (PLGA)-to-drug ratios (6:1 and 4:1) were manufactured through the electrospinning technology. The in vitro release behavior of imiquimod and metronidazole was evaluated via an elution method, while the in vivo discharge behavior was evaluated on a mice model. Additionally, a model of cervical cancer was established using C57BL/6J mice, and it was utilized to evaluate the efficacy of drug-eluting nanofibers through in vivo testing. Mice afflicted with cervical cancer were separated into three distinct groups for the study: The mice in Group A served as the control and received no treatment. Group B received treatment with pure PLGA nanofibers (no drugs loaded), whereas Group C received treatment with nanofibers loaded with imiquimod and metronidazole. Post implantation, the variations in tumor sizes of rats receiving the implantation of drug-eluting nanofibers were monitored.Results: The experimental data show that drug-eluting nanofibers could discharge in vitro high concentrations of imiquimod and metronidazole for exceeding 30 days. In vivo, each membrane consistently released elevated concentrations of imiquimod/metronidazole at the intended site in mice over a four-week period, with minimal systemic drug concentration detected in the bloodstream. The mice treated with drug-loaded nanofibers displayed noticeably reduced tumor volumes compared to both the control group and the group treated with pristine nanofibers. Histological examination revealed the absence of any discernible tissue inflammation.Conclusion: Biodegradable nanofibers with a sustainable release of imiquimod and metronidazole demonstrated their effectiveness and lasting impact of treating mice with cervical cancer.Keywords: cervical cancer, degradable nanofibers, imiquimod, metronidazole, extended drug releasehttps://www.dovepress.com/conglomerated-imiquimod-and-metronidazole-incorporated-biodegradable-n-peer-reviewed-fulltext-article-IJNcervical cancerdegradable nanofibersimiquimodmetronidazoleextended drug release |
| spellingShingle | Chen YP Chiu CF Wang CN Lin CC Shen CR Yao YC Kuo YH Liu SJ Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer International Journal of Nanomedicine cervical cancer degradable nanofibers imiquimod metronidazole extended drug release |
| title | Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer |
| title_full | Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer |
| title_fullStr | Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer |
| title_full_unstemmed | Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer |
| title_short | Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer |
| title_sort | conglomerated imiquimod and metronidazole incorporated biodegradable nanofibrous mats for potential therapy of cervical cancer |
| topic | cervical cancer degradable nanofibers imiquimod metronidazole extended drug release |
| url | https://www.dovepress.com/conglomerated-imiquimod-and-metronidazole-incorporated-biodegradable-n-peer-reviewed-fulltext-article-IJN |
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