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Development and Validation of PEG‐PCL Based Nanoformulation of Rosiglitazone and Evaluation of its Brain Selectivity in Mice Model of Alzheimer’s disease
Author(s) -
K C Sarathlal,
Kakoty Violina K,
Taliyan Rajeev
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.058674
Subject(s) - rosiglitazone , morris water navigation task , streptozotocin , endocrinology , medicine , oxidative stress , chemistry , pharmacology , adiponectin , hippocampus , insulin , diabetes mellitus , insulin resistance
Background Type‐2 Diabetes Mellitus and insulin resistance increases the risk of Alzheimer’s disease (AD). Recent studies highlighted the role of peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) in modulation of AD. This study was designed to investigate the effect of rosiglitazone alone or in its nanoformulated form for an effective drug delivery in mice model of AD. Method AD mice model was developed by intracerebroventricular (ICV) administration of streptozotocin (STZ). PEG‐PCL polymer was synthesized using ring opening polymerization of caprolactone with methoxy‐PEG as a macroinitiator and stannousoctoate as catalyst. Nanoformulation of rosiglitazone was developed using emulsion‐diffusion‐solvent evaporation method. Nanoformulation was evaluated by Scanning electron microscopy, particle size analyzer and HPLC method. Cognitive functions were evaluated by passive avoidance task, object recognition task and Morris water maze test. Amyloid beta (Aβ) and phosphorylated tau (p‐tau) level were assessed by ELISA, level of oxidative stress and pro‐inflammatory cytokines like tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) were measured in hippocampus homogenates and the expression level of CREB, BDNF, GDNF, NGF were assessed by RT‐PCR method. Result The rosiglitazone nanoformulation was observed within a range of 70±10 nm in size and the entrapment efficiency of rosiglitazone was 70±5%. The ICV‐STZ mice showed significant features of cognitive abnormalities. The mice treated with rosiglitazone and its formulation improved cognition, attenuated the elevated level of Aβ and p‐tau along with pro‐inflammatory cytokines‐TNF‐α and IL‐6 and oxidative stress was altered when compared with disease control animals. Moreover, these changes occurred concurrently with an increased expression level of BDNF, GDNF and NGF. Conclusion Nanoformulation of rosiglitazone imparted significant neuroprotective efficacy with greater amounts being observed in the brain at a lower dose compared to its free form.