Mucoadhesive and mucus-penetrating interpolyelectrolyte complexes for nose-to-brain drug delivery

Nanomedicine. 2021 Oct:37:102432. doi: 10.1016/j.nano.2021.102432. Epub 2021 Jun 27.

Abstract

Nasal administration offers a possibility of delivering drugs to the brain. In the present work, nasal drug delivery systems were designed based on cationic Eudragit® EPO (EPO) and anionic Eudragit® L100-55 (L100-55) methacrylate copolymers. Two types of nanocarriers were prepared using interpolyelectrolyte complexation between these polymers. The first type of nanoparticles was prepared by forming interpolyelectrolyte complexes between unmodified EPO and L100-55. The second type of nanoparticles was formed through the complexation between PEGylated L100-55 and EPO. For this purpose, PEGylated L100-55 was synthesized by chemical conjugation of L100-55 with O-(2-aminoethyl)polyethylene glycol. The mucoadhesive properties of these nanoparticles were evaluated ex vivo using sheep nasal mucosa. Nanoparticles based on EPO and L100-55 exhibited mucoadhesive properties towards nasal mucosa, whereas PEGylated nanoparticles were non-mucoadhesive hence displayed mucus-penetrating properties. Both types of nanoparticles were used to formulate haloperidol and their ability to deliver the drug to the brain was evaluated in rats in vivo.

Keywords: Eudragit®; Interpolyelectrolyte complex; Mucoadhesion; Nanoparticles; Nasal drug delivery; Nose-to-brain delivery.

MeSH terms

  • Acrylic Resins / chemistry
  • Acrylic Resins / pharmacology
  • Administration, Intranasal
  • Animals
  • Brain / drug effects*
  • Drug Delivery Systems*
  • Humans
  • Mucus / drug effects
  • Nanoparticles / chemistry*
  • Nasal Mucosa / drug effects
  • Polyelectrolytes / chemistry
  • Polyelectrolytes / pharmacology*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Polymers / chemistry
  • Polymers / pharmacology
  • Polymethacrylic Acids / chemistry
  • Polymethacrylic Acids / pharmacology
  • Sheep
  • Solubility / drug effects

Substances

  • Acrylic Resins
  • Eudragit L100-55
  • Polyelectrolytes
  • Polymers
  • Polymethacrylic Acids
  • Polyethylene Glycols
  • Eudragit E PO