Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins

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Drago , S E , Craparo , E F , Luxenhofer , R & Cavallaro , G 2021 , ' Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins ' , Nanomedicine: Nanotechnology, Biology and Medicine , vol. 37 , 102451 . https://doi.org/10.1016/j.nano.2021.102451

Title: Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins
Author: Drago, Salvatore E.; Craparo, Emanuela F.; Luxenhofer, Robert; Cavallaro, Gennara
Contributor organization: Helsinki Institute of Sustainability Science (HELSUS)
Polymers
Department of Chemistry
Date: 2021-10
Language: eng
Number of pages: 15
Belongs to series: Nanomedicine: Nanotechnology, Biology and Medicine
ISSN: 1549-9634
DOI: https://doi.org/10.1016/j.nano.2021.102451
URI: http://hdl.handle.net/10138/346429
Abstract: In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy was applied, encapsulating the nanoparticles in water-soluble mannitol-based microparticles by spray-drying. This process has allowed to produce spherical microparticles with the proper size for optimal lung deposition, and, once in contact with fluids mimicking the lung district, able to dissolve and release non-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24hours.
Subject: 116 Chemical sciences
Poly(2-oxazoline)s
Poly(2-oxazine)s
Polyaspartamide
Polylactic acid
Zileuton
Nanoparticles
Lung inflammation
POLYASPARTAMIDE
DRUG-DELIVERY
PULMONARY DELIVERY
POLY(2-OXAZOLINE)S
RELEASE
AIRWAY MUCUS
CHALLENGES
INHIBITION
ASTHMA
DIFFUSION
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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