Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington's disease via the nasal-brain route.

作者信息

Singla Madhav, Gupta Saurabh, Porwal Omji, Nasser Binjawhar Dalal, Sayed Amany A, Mittal Pooja, El-Demerdash Fatma M, Algahtani Mohammad, Singh Sachin Kumar, Dua Kamal, Gupta Gaurav, Bawa Puneet, Altyar Ahmed E, Abdel-Daim Mohamed M

机构信息

Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.

Chameli Devi Institute of Pharmacy, Department of Pharmacology, Indore, Madhya Pradesh.

出版信息

Front Pharmacol. 2023 Jul 10;14:1218625. doi: 10.3389/fphar.2023.1218625. eCollection 2023.

Abstract

To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington's disease (HD). We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability. HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain's motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD. The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

摘要

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索