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

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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,Laspartamide(PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among varioustested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowestdimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy wasapplied, encapsulating the nanoparticles in water-solublemannitol-basedmicroparticles by spray-drying. This process has allowed to produce sphericalmicroparticles with the proper size for optimal lung deposition, and, once in contactwith fluidsmimicking the lung district, able to dissolve and releasenon-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24 h.
Lingua originaleEnglish
pagine (da-a)1-15
Numero di pagine15
RivistaNANOMEDICINE
Volume37
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

  • ???subjectarea.asjc.1500.1502???
  • ???subjectarea.asjc.2700.2701???
  • ???subjectarea.asjc.1300.1313???
  • ???subjectarea.asjc.2200.2204???
  • ???subjectarea.asjc.2500.2500???
  • ???subjectarea.asjc.3000.3003???

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