PMID- 32334065
OWN - NLM
STAT- MEDLINE
DCOM- 20210210
LR  - 20210616
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 583
DP  - 2020 Jun 15
TI  - Treatment of insulin resistance in obesity-associated type 2 diabetes mellitus 
      through adiponectin gene therapy.
PG  - 119357
LID - S0378-5173(20)30341-0 [pii]
LID - 10.1016/j.ijpharm.2020.119357 [doi]
AB  - Global rise in obesity-associated type 2 diabetes mellitus (T2DM) has led to a 
      major healthcare crisis. Development of efficient treatments to treat the 
      underlying chronic inflammation in obesity-associated T2DM, is an unmet medical 
      need. To this end, we have developed a plasmid adiponectin (pADN) based 
      nanomedicine for the treatment of insulin resistance in type 2 diabetes mellitus. 
      Adiponectin is a potent anti-inflammatory/anti-diabetic adipokine, which is 
      downregulated in obesity. In this study, nanomicelles comprising chitosan 
      conjugated to oleic acid and adipose homing peptide (AHP) were developed to 
      deliver pADN to adipocytes. Cationic chitosan-oleic-AHP micelles were 112 nm in 
      size, encapsulated 93% of pADN and protected gene cargo from DNase I mediated 
      enzymatic degradation. In vitro, the nanomicellar formulation significantly 
      increased adiponectin production compared to free plasmid as well as standard 
      transfecting agent FuGENE(R)HD. Single dose subcutaneous administration of 
      pADN-chitosan-oleic-AHP to obese-diabetic rats, resulted in improved insulin 
      sensitivity for up to 6 weeks, which matched the glucose disposal ability of 
      healthy rats. Serum adiponectin level in pADN-chitosan-oleic-AHP treated rats was 
      comparable to healthy rats for up to 3 weeks post treatment. Overall, the results 
      indicate that pADN-chitosan-oleic-AHP based therapy is a promising treatment 
      approach for obesity-associated T2DM.
CI  - Published by Elsevier B.V.
FAU - Banerjee, Amrita
AU  - Banerjee A
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo 58105, ND, USA. Electronic 
      address: amrita.banerjee@ndsu.edu.
FAU - Sharma, Divya
AU  - Sharma D
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo 58105, ND, USA.
FAU - Trivedi, Riddhi
AU  - Trivedi R
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo 58105, ND, USA.
FAU - Singh, Jagdish
AU  - Singh J
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, College of Health 
      Professions, North Dakota State University, Fargo 58105, ND, USA. Electronic 
      address: jagdish.singh@ndsu.edu.
LA  - eng
GR  - R15 GM114701/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20200422
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Adiponectin)
RN  - 0 (Peptides)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adiponectin/blood/*genetics
MH  - Animals
MH  - Chitosan/*administration & dosage
MH  - Diabetes Mellitus, Experimental/etiology/*therapy
MH  - Diabetes Mellitus, Type 2/etiology/*therapy
MH  - Genetic Therapy
MH  - *Insulin Resistance
MH  - Male
MH  - Mice
MH  - Nanoparticles/*administration & dosage
MH  - Obesity/complications/therapy
MH  - Oleic Acid/*administration & dosage
MH  - Peptides/*administration & dosage
MH  - Plasmids
MH  - Rats, Wistar
PMC - PMC7261390
MID - NIHMS1588605
OTO - NOTNLM
OT  - Adiponectin
OT  - Chitosan nanoparticles
OT  - Gene therapy
OT  - Insulin resistance
OT  - Type 2 diabetes mellitus
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/04/26 06:00
MHDA- 2021/02/11 06:00
PMCR- 2021/06/15
CRDT- 2020/04/26 06:00
PHST- 2020/01/09 00:00 [received]
PHST- 2020/04/13 00:00 [revised]
PHST- 2020/04/19 00:00 [accepted]
PHST- 2020/04/26 06:00 [pubmed]
PHST- 2021/02/11 06:00 [medline]
PHST- 2020/04/26 06:00 [entrez]
PHST- 2021/06/15 00:00 [pmc-release]
AID - S0378-5173(20)30341-0 [pii]
AID - 10.1016/j.ijpharm.2020.119357 [doi]
PST - ppublish
SO  - Int J Pharm. 2020 Jun 15;583:119357. doi: 10.1016/j.ijpharm.2020.119357. Epub 
      2020 Apr 22.