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

• DOI: 10.1016/j.nano.2021.102432
• Publication Date: 2021-06-27T09:09:46Z
• Authors: Natalia N. Porfir...; Irina I. Semina; Ilgiz A. Salakhov; Rouslan I. Mousta...; Vitaliy V. Khutor...
• Keywords: Nanocarriers; Mucoadhesion

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.