• Evaluation of trend drugs loaded in lipid nanoparticles in Alzheimer’s disease: benefits, challenges and administration route
  • Sayed Mehrdad Azimi,1,* Jaleh Varshosaz,2 Hamid Bahramian,3
    1. Department of Anatomical and Molecular Biology Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
    2. Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
    3. Department of Anatomical and Molecular Biology Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


  • Introduction: Alzheimer's disease (AD) is the most common form of dementia, affecting about 50 million people worldwide prevalence. Accumulation of amyloid-beta plaques and neurofibrillary tangles containing tau protein in the brain is the hallmark pathologies of this progressive neurodegenerative disease that leads to neuronal dysfunction and loss. No current treatments can halt or reverse the progression of AD because the blood-brain barrier (BBB) is an obstacle to the transport of therapeutic agents to the brain. Lipid nanoparticles such as liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) have shown promise as drug delivery systems to improve transport across the BBB. Encapsulation of drugs in lipid nanoparticles protects cargo, increases solubility, controls release rate, and may facilitate uptake into the brain through receptor-mediated transcytosis. Many small molecule drugs, peptides, proteins, siRNA, and metal-based agents with therapeutic potential for AD are being incorporated into lipid nanoparticles to test their efficacy after targeted delivery to the brain. This review evaluates and introduces a comprehensive list for trend drugs loaded on lipid nanoparticle technology to deliver for AD candidates. The benefits and challenges of this nanomedicine approach to AD will be discussed, along with the administration routes to determine the impact of in vivo efficacy of nanoparticle drug delivery for AD treatment.
  • Methods: A complete search strategy was assigned to identify relevant articles based on keywords including drugs, lipid nanoparticles, and Alzheimer’s disease and related keywords. PubMed, Web of Science, Scopus, and Google Scholar as popular databases were searched for articles published from 2018 to 2023. The articles were skimmed by two reviewers separately, based on title/ abstract. All relevant studies were included. Unrelated and non-English articles were excluded and listed.
  • Results: Based on recent investigations, a wide variety of small molecule drugs, biologics, and genetic materials are being actively explored using lipid nanoparticle delivery systems for potential Alzheimer's therapy. These drugs include curcumin, resveratrol, selenium, coenzyme-Q10 (with anti-inflammatory and antioxidant properties), exendin-4 (A glucagon-like peptide-1 agonist for AD diabetic patients), and some anti-amyloid drugs like statins, simvastatin, doxorubicin, cilostazol, anti-amyloid antibodies, and siRNA. Investigations indicate some inhibitor drugs for acetylcholinesterase, phosphodiesterase, histone deacetylase and angiotensin receptor including tacrine, rivastigmine, cilostazol, phenylbutyrate and telmisartan are useful in AD patients respectively. Researchers confirm some naturally secreted hormones (e.g., estrogen, melatonin, and pregnenolone) can positively impact your overall memory and cognitive function. On the other side of the review, common administration routes for drug delivery include oral, ocular, and intranasal (IN) administration, intravenous and intraventricular/intrathecal injection, and transdermal patches are listed. The non-invasive oral and nasal routes and intravenous administration seem to be among the most promising approaches for using lipid nanoparticles to deliver drugs for AD treatment. Overall, IN administration seems to offer direct brain targeting, a non-invasive and suitable route for a vast range of drugs loaded on lipid nanoparticles.
  • Conclusion: As the results indicated, the most of the drugs are bioavailable to load on lipid nanoparticles which are listed in this review. It should be noted that according to the AD pathogenesis, the drugs chosen. In this way, the most challenge is to administrate and optimize the drug delivery route. When comparing administration routes for drug delivery in AD treatment, there is no definitive "best" option. Each route has different pros and cons in terms of invasiveness, ability to cross the blood-brain barrier, targeted delivery, patient compliance, and suitability for certain drug formulations. Investigations indicate that IN administration is better than others. It appears a promising route as provides direct access to the brain. Besides challenges such as low bioavailability, toxic contaminants, high variability, etc. which require careful formulation strategies using absorption enhancers, optimized delivery devices, enzyme inhibitors, and nanoparticles like liposomes that can protect drugs and modulate transport.
  • Keywords: Lipid Nanoparticles, Alzheimer disease, Drug Delivery Systems, Intranasal Administration