Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice
Tuyet-Nhi Do,1 Yen-Chin Liu,2– 4 Yu-Che Chuang,5 Tsung-Lin Tsai,1,6,7 Ping-Ching Wu1,6,8– 10 1Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, 701, Taiwan; 2School of Post-Baccalaureate, College of Medicine, Kaohsiung Medical University, Kaohsiung...
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Dove Medical Press
2025-06-01
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| author | Do TN Liu YC Chuang YC Tsai TL Wu PC |
| author_facet | Do TN Liu YC Chuang YC Tsai TL Wu PC |
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| description | Tuyet-Nhi Do,1 Yen-Chin Liu,2– 4 Yu-Che Chuang,5 Tsung-Lin Tsai,1,6,7 Ping-Ching Wu1,6,8– 10 1Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, 701, Taiwan; 2School of Post-Baccalaureate, College of Medicine, Kaohsiung Medical University, Kaohsiung, 812, Taiwan; 3Department of Anesthesiology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 812, Taiwan; 4Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 5Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan; 6Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan; 7Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 8Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 9Medical Device Innovation Center, Taiwan Innovation Center of Medical Devices and Technology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, 701, Taiwan; 10University Center of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, TaiwanCorrespondence: Ping-Ching Wu, Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, Email wbcxyz@gmail.com Tsung-Lin Tsai, Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan, Email sloantsai@mail.ncku.edu.twIntroduction: Chronic pain is a complex condition that requires timely and effective management to prevent long-term emotional, social, and economic consequences. This study aims to develop a poly(lactic-co-glycolic acid) (PLGA)-based nanocomposite co-loaded with ketorolac tromethamine (KT) and prednisolone (PRED) to improve therapeutic efficacy and reduce systemic side effects associated with conventional treatments.Methods: KT-PRED-PLGA nanoparticles were synthesized via a double emulsion method and characterized for their physicochemical properties and biocompatibility. A chronic inflammatory pain model was established in ICR mice using Complete Freund’s Adjuvant (CFA). Mechanical pain thresholds were evaluated using Dixon’s up-and-down method. Histopathological and immunohistochemical analyses were performed to evaluate systemic toxicity and inflammation-related protein expression.Results: The KT-PRED-PLGA nanoparticles exhibited favorable characteristics, including a mean particle size of 166.2 ± 8.0 nm, a polydispersity index of 0.14, a zeta potential of − 15.8 ± 0.3 mV, and encapsulation efficiency exceeding 80%. The nanoparticles sustained drug release up to 92.5% over 120 h. In vitro assays demonstrated the KT-PRED-PLGA nanoparticles revealed high biocompatibility in Vero cells after 72 h of exposure. In vivo experiments demonstrated significantly reduced pain behaviors and tissue inflammation, with minimal toxicity. Behavioral assessments confirmed enhanced analgesic and anti-allodynic effects over the free drugs. Reduced expression of cyclooxygenases (COX-1 and COX-2) and prostaglandin E2 (PGE2) in hind paw tissues confirmed improved anti-inflammatory activity.Conclusion: KT-PRED-PLGA nanoparticles offer safe, sustained analgesia with enhanced therapeutic efficacy and reduced systemic toxicity, highlighting their strong potential for future clinical translation in chronic pain therapy. Keywords: ketorolac tromethamine and prednisolone encapsulation, PLGA nanoparticle drug delivery, nanomedicine, double emulsion strategy, chronic inflammatory pain relief |
| format | Article |
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| language | English |
| publishDate | 2025-06-01 |
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| series | International Journal of Nanomedicine |
| spelling | doaj-art-1b9f1e821c4449519e9d4a688bae2f702025-06-26T23:29:10ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-06-01Volume 20Issue 183438357104284Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in MiceDo TN0Liu YC1Chuang YC2Tsai TL3Wu PC4Department of Biomedical EngineeringDepartment of AnesthesiologyDepartment of Pathology and Laboratory MedicineDepartment of Oncology, National Cheng Kung University Hospital, College of MedicineDepartment of Biomedical EngineeringTuyet-Nhi Do,1 Yen-Chin Liu,2– 4 Yu-Che Chuang,5 Tsung-Lin Tsai,1,6,7 Ping-Ching Wu1,6,8– 10 1Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, 701, Taiwan; 2School of Post-Baccalaureate, College of Medicine, Kaohsiung Medical University, Kaohsiung, 812, Taiwan; 3Department of Anesthesiology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 812, Taiwan; 4Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 5Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan; 6Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan; 7Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 8Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 9Medical Device Innovation Center, Taiwan Innovation Center of Medical Devices and Technology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, 701, Taiwan; 10University Center of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, TaiwanCorrespondence: Ping-Ching Wu, Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, Email wbcxyz@gmail.com Tsung-Lin Tsai, Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan, Email sloantsai@mail.ncku.edu.twIntroduction: Chronic pain is a complex condition that requires timely and effective management to prevent long-term emotional, social, and economic consequences. This study aims to develop a poly(lactic-co-glycolic acid) (PLGA)-based nanocomposite co-loaded with ketorolac tromethamine (KT) and prednisolone (PRED) to improve therapeutic efficacy and reduce systemic side effects associated with conventional treatments.Methods: KT-PRED-PLGA nanoparticles were synthesized via a double emulsion method and characterized for their physicochemical properties and biocompatibility. A chronic inflammatory pain model was established in ICR mice using Complete Freund’s Adjuvant (CFA). Mechanical pain thresholds were evaluated using Dixon’s up-and-down method. Histopathological and immunohistochemical analyses were performed to evaluate systemic toxicity and inflammation-related protein expression.Results: The KT-PRED-PLGA nanoparticles exhibited favorable characteristics, including a mean particle size of 166.2 ± 8.0 nm, a polydispersity index of 0.14, a zeta potential of − 15.8 ± 0.3 mV, and encapsulation efficiency exceeding 80%. The nanoparticles sustained drug release up to 92.5% over 120 h. In vitro assays demonstrated the KT-PRED-PLGA nanoparticles revealed high biocompatibility in Vero cells after 72 h of exposure. In vivo experiments demonstrated significantly reduced pain behaviors and tissue inflammation, with minimal toxicity. Behavioral assessments confirmed enhanced analgesic and anti-allodynic effects over the free drugs. Reduced expression of cyclooxygenases (COX-1 and COX-2) and prostaglandin E2 (PGE2) in hind paw tissues confirmed improved anti-inflammatory activity.Conclusion: KT-PRED-PLGA nanoparticles offer safe, sustained analgesia with enhanced therapeutic efficacy and reduced systemic toxicity, highlighting their strong potential for future clinical translation in chronic pain therapy. Keywords: ketorolac tromethamine and prednisolone encapsulation, PLGA nanoparticle drug delivery, nanomedicine, double emulsion strategy, chronic inflammatory pain reliefhttps://www.dovepress.com/combination-of-ketorolac-tromethamine-and-prednisolone-loaded-plga-nan-peer-reviewed-fulltext-article-IJNKetorolac tromethamine and prednisolone encapsulationPLGA nanoparticle drug deliveryNanomedicineDouble emulsion strategyChronic inflammatory pain relief. |
| spellingShingle | Do TN Liu YC Chuang YC Tsai TL Wu PC Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice International Journal of Nanomedicine Ketorolac tromethamine and prednisolone encapsulation PLGA nanoparticle drug delivery Nanomedicine Double emulsion strategy Chronic inflammatory pain relief. |
| title | Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice |
| title_full | Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice |
| title_fullStr | Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice |
| title_full_unstemmed | Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice |
| title_short | Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice |
| title_sort | combination of ketorolac tromethamine and prednisolone loaded plga nanocomposite for effective chronic pain relief in mice |
| topic | Ketorolac tromethamine and prednisolone encapsulation PLGA nanoparticle drug delivery Nanomedicine Double emulsion strategy Chronic inflammatory pain relief. |
| url | https://www.dovepress.com/combination-of-ketorolac-tromethamine-and-prednisolone-loaded-plga-nan-peer-reviewed-fulltext-article-IJN |
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