Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment
Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designe...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522005238 |
| _version_ | 1827897767606878208 |
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| author | Lin Hou Xueyuan Peng Ruiting Wang Yifei Wang Hong Li Huijuan Zhang Yun Zhang Zhenzhong Zhang |
| author_facet | Lin Hou Xueyuan Peng Ruiting Wang Yifei Wang Hong Li Huijuan Zhang Yun Zhang Zhenzhong Zhang |
| author_sort | Lin Hou |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment. |
| first_indexed | 2024-03-12T22:53:26Z |
| format | Article |
| id | doaj.art-d23ef4fa19734b41a60ae3ebf6fffc36 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-12T22:53:26Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-d23ef4fa19734b41a60ae3ebf6fffc362023-07-20T04:38:23ZengElsevierActa Pharmaceutica Sinica B2211-38352023-07-0113731373152Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatmentLin Hou0Xueyuan Peng1Ruiting Wang2Yifei Wang3Hong Li4Huijuan Zhang5Yun Zhang6Zhenzhong Zhang7School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China; Corresponding authors.School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China; Corresponding authors.School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, China; Corresponding authors.School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001, ChinaType 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.http://www.sciencedirect.com/science/article/pii/S2211383522005238Type 2 diabetes mellitusOral drug deliveryPLGA nanoparticlesPancreatic islet β-cellsLymphatic transportationTaurocholic acid |
| spellingShingle | Lin Hou Xueyuan Peng Ruiting Wang Yifei Wang Hong Li Huijuan Zhang Yun Zhang Zhenzhong Zhang Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment Acta Pharmaceutica Sinica B Type 2 diabetes mellitus Oral drug delivery PLGA nanoparticles Pancreatic islet β-cells Lymphatic transportation Taurocholic acid |
| title | Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment |
| title_full | Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment |
| title_fullStr | Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment |
| title_full_unstemmed | Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment |
| title_short | Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment |
| title_sort | oral nano formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment |
| topic | Type 2 diabetes mellitus Oral drug delivery PLGA nanoparticles Pancreatic islet β-cells Lymphatic transportation Taurocholic acid |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522005238 |
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