In:
Current Drug Metabolism, Bentham Science Publishers Ltd., Vol. 23, No. 7 ( 2022-06), p. 571-583
Abstract:
Diabetic peripheral neuropathy is the most common complication of diabetes mellitus.
Epalrestat, an aldose reductase inhibitor, has been approved for clinical therapy for diabetic peripheral neuropathic pain. In the present study, solid lipid-based nanoparticles are used for oral administration of epalrestat (E-SLN) and
evaluated against diabetic neuropathic pain in a rat model. Method: Experimental diabetes in rats was induced by a single dose of streptozotocin (STZ) administration. The therapeutic efficiency of Epalrestat nanoparticles (0.25, 0.50, 1, and 5 mg/kg) in diabetic rats was studied. STZ induced diabetic rats were treated with different doses of E-SLN for 8 weeks. The nanoparticles were orally administered at a single dose in rats, and the various parameters related to peripheral neuropathy were evaluated and compared with the bare drug. The blood glucose level was estimated by standard glucometer, HbA1c, triglycerides, total cholesterol and liver function test (ALT and AST) were analysed by blood samples collected from retro-orbital plexus. Oxidative stress markers and Na+K+ATPase, TNF- & @945; and IL-1β levels were measured in the homogenate of sciatic nerves. Behavioural tests were also performed by the hot plate method and tail-flick method. Result: E-SLN synthesized by the micro-emulsification method was 281 ± 60 nm in size, and encapsulation efficacy
was found to be 88 ± 2%. Optimized E-SLN were characterized and found to be optimum in size, spherical shape, decent encapsulation efficiency, stable at acidic gastric pH, and suitable for oral delivery. E-SLNs did not significantly
reverse the STZ-induced elevated blood glucose level (FBS and PPBS), HbA1c, triglycerides, and total cholesterol but significantly improved TNF-α, IL-1β, and increased Na+K+ATPase levels, oxidative stress marker and ALT, AST
in the treated rat group as compared with the diabetic group. Doses of E-SLN, i.e. 0.5, 1.0, 2.5, and 5 mg/kg, significantly increased the tail-flick latency time and hot plate response time in a dose-dependent manner compared with
the diabetic group. Conclusion: Thus, it is suggested that E-SLN were equally effective and less hepatotoxic compared with the standard
treatment of epalrestat. To the best of our knowledge, we, for the first time, propose the orally deliverable E-SLN that ameliorates STZ-induced diabetes neuropathic pain effectively as compared with conventional epalrestat.
Type of Medium:
Online Resource
ISSN:
1389-2002
DOI:
10.2174/1389200223666220810152633
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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