Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles

Abstract

Recently, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both clinical and pharmaceutical fields. In this review, we summarize our studies evaluating nose-to-brain delivery of drugs and small interfering ribonucleic acids in combination with cell-penetrating peptide-modified polymer micelles. Our findings show that the use of polymer micelles with surface modification with Tat peptide in the intranasal administration enables the non-invasive delivery of therapeutic agents to the brain by increasing the transfer of the administered drug or small interfering ribonucleic acid to the central nervous system from the nasal cavity.

Intelligent micellar polymeric nanocarriers for therapeutics and diagnosis

“…From the lessons learned from the experience gained in cancer research and the possibility of combining different elements (e.g., drugs, antibodies, nucleic acids, imaging contrasts agents, targeting ligands, inorganic NPs), the search for different multifunctionalities within a single polymeric micelle should additionally expand the vast available range of prospective nanodevices to imaging and should look toward treating not only cancerous cells and tissues but also other diseases that target tissues of interest, such as the liver, lungs, bones, stroke sites, and ischemic myocardium, with appropriate targeting ligands to treat diseases such as human immunodeficiency virus, tuberculosis, arthritis, and infarctions, among others, to also make use of alternative administration routes, such as oral, ocular, and intranasal routes . For example, BCMs encapsulated with potent antibiotics and decorated with suitable ligands against the cell surface proteins of microbes and parasites or able to protect small RNAs may revolutionize the treatment of many globally important infection or protein‐related diseases, respectively.…”

Nanopharmaceuticals: A Boon to the Brain-Targeted Drug Delivery

“…Another polymer methoxy-PEG-polycaprolactone was used to encapsulate coumarin with promising brain penetration and myelin binding properties, while administered through nasal route [58]. Bioadhesive nanocarriers reported in the above studies overcome many hurdles associated with a nasal route like protection of drug against enzymatic degradation, enhanced permeability, and avoidance of mucociliary clearance.…”

Application of nanomedicine for crossing the blood–brain barrier: Theranostic opportunities in multiple sclerosis

“…These nanoscale micelles have been used as carriers in therapeutic systems (Jang et al 2006). Regarding the small size of these carriers, they can transport drugs across neurons to the brain via endocytosis (Kanazawa 2015). Polymeric micelles composed of Pluronic block co-polymers (also termed poloxamer) are effective carriers for hydrophobic drugs with long-circulating characteristics via inhibition of phagocytosis by the reticuloendothelial system (Batrakova & Kabanov 2008).…”

“…It seems that conjugation of the CPP to the surface of nanocarriers can increase their penetration across the nasal mucosa and target cell membranes in the brain (Kanazawa 2015). Conjugation of MPEG-PCL micelles with Tat peptide (MPEG-PCL-Tat) enhanced the intranasal brain delivery of coumarin in rats (Kanazawa et al 2011).…”