PMID- 37521855
OWN - NLM
STAT- Publisher
LR  - 20230801
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 13
IP  - 7
DP  - 2023 Jul
TI  - Oral nano-formulation improves pancreatic islets dysfunction via lymphatic 
      transport for antidiabetic treatment.
PG  - 3137-3152
LID - 10.1016/j.apsb.2022.12.014 [doi]
AB  - Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term 
      medication and gradual destruction of pancreatic islet beta-cells. Therefore, it is 
      timely to develop oral prolonged action formulations to improve compliance, while 
      restoring beta-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.
CI  - (c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Hou, Lin
AU  - Hou L
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
AD  - Collaborative Innovation Center of New Drug Research and Safety Evaluation, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Peng, Xueyuan
AU  - Peng X
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Wang, Ruiting
AU  - Wang R
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Wang, Yifei
AU  - Wang Y
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Li, Hong
AU  - Li H
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Zhang, Huijuan
AU  - Zhang H
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
AD  - Collaborative Innovation Center of New Drug Research and Safety Evaluation, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
AD  - Collaborative Innovation Center of New Drug Research and Safety Evaluation, 
      Zhengzhou University, Zhengzhou 450001, China.
FAU - Zhang, Zhenzhong
AU  - Zhang Z
AD  - School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
AD  - Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, 
      Zhengzhou University, Zhengzhou 450001, China.
AD  - Collaborative Innovation Center of New Drug Research and Safety Evaluation, 
      Zhengzhou University, Zhengzhou 450001, China.
LA  - eng
PT  - Journal Article
DEP - 20221222
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC10373096
OTO - NOTNLM
OT  - Hydroxychloroquine
OT  - Lymphatic transportation
OT  - Oral drug delivery
OT  - PLGA nanoparticles
OT  - Pancreas microenvironment
OT  - Pancreatic islet beta-cells
OT  - Taurocholic acid
OT  - Type 2 diabetes mellitus
EDAT- 2023/07/31 06:42
MHDA- 2023/07/31 06:42
PMCR- 2022/12/22
CRDT- 2023/07/31 05:14
PHST- 2022/08/15 00:00 [received]
PHST- 2022/10/20 00:00 [revised]
PHST- 2022/11/08 00:00 [accepted]
PHST- 2023/07/31 06:42 [medline]
PHST- 2023/07/31 06:42 [pubmed]
PHST- 2023/07/31 05:14 [entrez]
PHST- 2022/12/22 00:00 [pmc-release]
AID - S2211-3835(22)00523-8 [pii]
AID - 10.1016/j.apsb.2022.12.014 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2023 Jul;13(7):3137-3152. doi: 10.1016/j.apsb.2022.12.014. Epub 
      2022 Dec 22.