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The Pharma Innovation Journal 2018; 7(1): 482-485
ISSN (E): 2277- 7695
ISSN (P): 2349-8242
NAAS Rating: 5.03
TPI 2018; 7(1): 482-485
© 2018 TPI
www.thepharmajournal.com
Received: 01-11-2017
Accepted: 02-12-2017
Pooja Verma
Assistant Professor, School of
Medical & Allied Sciences, G.D
Goenka University, Gurgaon,
Haryana, India
Correspondence
Pooja Verma
Assistant Professor, School of
Medical & Allied Sciences, G.D
Goenka University, Gurgaon,
Haryana, India
Effect of alpha-lipoic acid and its Nano-formulation on
streptozotocin induced diabetic neuropathy in Rats
Pooja Verma
Abstract
Diabetic Neuropathy is the most prevalent and costly complication of hyperglycemia that is affecting half
of the patient worldwide and its incidence rate has increased upto several folds. It includes impairment of
pain signalling pathways. The aim of the investigation was to determine the effect of alpha-lipoic acid in
Streptozotocin induced diabetic neuropathic pain in rats by oral route, intraperitoneal route, Preparation
of nano-emulsion of alpha lipoic acid and evaluate its effect by oral and intraperitoneal route as well as to
determine effect of alpha-lipoic acid on diabetes itself. Alpha-lipoic acid and its Nano-formulation was
orally and intraperitoneal administered to STZ induced diabetic rats for 3 weeks. Tail flick latency and
tail immersion test were done to determine thermal hyperalgesia, Randall-selitto paw pressure test to
determine mechanical hyperalgesia, von-frey hair to mechano-tactile allodynia and Hot plate for
mechanical nociception at different time intervals i.e., 2nd and 3rd week.
Keywords: Diabetic neuropathy, Nano-formulation, Allodynia, Hyperalgesia, Neuropathic pain
1. Introduction
Diabetes Mellitus is associated with oxidative stress in both animals and human beings. Long
term hyperglycaemia evokes enhanced polyol pathway, increased non-enzymatic glycation of
structural proteins, enhanced oxidative stress and in addition PKC activation all interrelated for
the cause and development of DN. Streptozotocin (STZ) induced diabetes is the most reliable
long term hyperglycaemic model which is considered to be most stable. The mechanism of
STZ is still unclear but several times it is reported that it causes pancreatic cell destruction by
undergoing methylation through damaging the DNA.
The current mainstream drugs for treatment of diabetic neuropathy includes antiepileptic
agents (gabapentin and pregabalin), selective serotonin reuptake inhibitors (SSRIs) and
tricyclic antidepressants are Food and Drug Administration (FDA) approved for the treatment
of DN. The drugs are largely included within the classifications of antidepressants,
anticonvulsants, antipsychotics, anaesthetics/anti-arrythmics, vasodilators, anti-dementia
agents, and opioids. For many of these medications, use for neuropathic pain is off-label; they
were approved by the Food and Drug Administration for other indications. Many are in the
news for questionable side effects (eg, increased blood pressure and oedema from salt
retention with fludrocortisones). So more researchers are turning towards the bioactive
compounds and herbal remedies to find the better pharmacotherapy for diabetic that will
negate the side effects usually associated with the current mainstream drug. Alpha-lipoic acid a
well-known antioxidant. It is known for its high chelating property with metal ions with doing
so oxidative induced due to iron is prevented. ALA increase the synthesis of GSH by
mediating gene expression induced by NrF. Also ALA is have the ability to increase nerve
regeneration and regeneration of antioxidants like vitamin c and GSH. Oral formulations of
Alpha-lipoic acid present problems due to characteristics of the molecule, Short blood half-life
(t1⁄2 ~ 30 minutes). It has poor solubility. Therefore resulting in low- Oral Bioavailability
30%Alpha-lipoic acid (ALA) is an important micronutrient with several pharmacologic as well
as antioxidant properties
[19]
. Oral formulations present problems due to characteristics of the
molecule and of the pharmaceutical forms. It is known that ALA is poorly soluble; therefore to
increase the solubility was reticulated into a Nano-emulsion formulation. Previously solubility
of alpha-lipoic acid is enhanced by techniques such as (microonisation and salification) but
these techniques possess several drawbacks. Therefore, in the present research. We are making
Nano-formulation particularly Nano-emulsion for bioavailability enhancement of alpha-lipoic
acid.