Mono-lithocholated exendin-4-loaded glycol chitosan nanoparticles with prolonged antidiabetic effects.
Hydrophobically modified glycol chitosan (HGC) nanoparticles loaded with mono-lithocholic acid-conjugated exendin-4 at the Lys(27) residue (LAM1-Ex4) were prepared and characterized by particle size measurement, proteolytic stability, in vitro drug-release profile, and in vivo antidiabetic effects in a db/db diabetic mouse model. Compared with Ex-4-loaded HGC nanoparticles (Ex4/HGC NPs) prepared as a control, LAM1-Ex4-loaded HGC nanoparticles (LAM1-Ex4/HGC NPs) showed improved drug-loading efficiency, small particle size, enhanced resistance against proteolytic digestion, and an extended in vitro drug release profile. These findings may be attributable to the strong hydrophobic interaction between LAM1-Ex4 and the inner core of HGC. Furthermore, LAM1-Ex4/HGC NPs showed prolonged hypoglycemic efficacy in db/db mice, lasting 1 week after a single subcutaneous administration. The present study demonstrated that LAM1-Ex4/HGC NPs have considerable potential as a long-acting sustained-release antidiabetic system for type 2 diabetes.
Drug Targeting Laboratory, School of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
Sohee
S
Son
Drug Targeting Laboratory, School of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
Sung Mook
SM
Lim
Drug Targeting Laboratory, School of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
Su Young
SY
Chae
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, Republic of Korea.
Kwangmeyung
K
Kim
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea.
Eun Ji
EJ
Park
Drug Targeting Laboratory, School of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-gu, Suwon 440-746, Republic of Korea. Electronic address: kclee@skku.edu.
Kang Choon
KC
Lee
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea. Electronic address: dhna@knu.ac.kr.
Dong Hee
DH
Na
D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D065546:Drug Liberation; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D008095:Lithocholic Acid / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D013388:Succinimides / Q000737:chemistry; D014688:Venoms / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*
D004337:Drug Carriers; D007004:Hypoglycemic Agents; D010455:Peptides; D013388:Succinimides; D014688:Venoms; C118638:glycol-chitosan; D008095:Lithocholic Acid; D048271:Chitosan; D000077270:Exenatide; D008239:Lysine; C001426:N-hydroxysuccinimide
Antidiabetic effects; Exendin-4; Glycol chitosan; Lithocholic acid; Nanoparticles