Glucose-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[5]arene and Pyridylboronic Acid Derivatives for Controlled Insulin Delivery.
The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus.
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Lei
L
Gao
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Tingting
T
Wang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, P. R. China.
Keke
K
Jia
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Xuan
X
Wu
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Chenhao
C
Yao
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Wei
W
Shao
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, P. R. China.
Dongmei
D
Zhang
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Xiao-Yu
XY
Hu
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.|Institute for Natural and Synthetic Organic Chemistry, Changzhou University, Changzhou, 213164, P. R. China.
Leyong
L
Wang
D001897:Boronic Acids / Q000737:chemistry*; D047250:Calixarenes; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013053:Spectrophotometry; D014867:Water / Q000737:chemistry
D001897:Boronic Acids; D004337:Drug Carriers; D007328:Insulin; D000644:Quaternary Ammonium Compounds; C031573:insulin, fluorescein-isothiocyanated-; C570642:pillar(5)arene; D014867:Water; D047250:Calixarenes; D004317:Doxorubicin; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose
diabetes; drug delivery; host-guest systems; supramolecular chemistry; vesicles