Inhalable Lactoferrin/Chondroitin-Functionalized Monoolein Nanocomposites for Localized Lung Cancer Targeting

Hadeer M. Abdelaziz, Ahmed O. Elzoghby*, Maged W. Helmy, Elsayeda Zeinab A. Abdelfattah, Jia You Fang, Magda W. Samaha, May S. Freag

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

28 Scopus citations

Abstract

Localized drug delivery to lung cancer can overcome the limitations of systemic nanocarriers including low drug amounts reaching lung tissues and severe off-target toxicity. The current work presented novel inhalable nanocomposites as noninvasive platforms for lung cancer therapy. Nanoparticulate liquid crystals (LCNPs) based on monoolein were developed for synergistic co-encapsulation of the cytotoxic chemotherapeutic drug, pemetrexed, and the phytoherbal drug, resveratrol (PEM-RES-LCNPs). For active tumor targeting, lactoferrin (LF) and chondroitin sulfate (CS), natural polymers with intrinsic tumor-targeting capabilities, were exploited to functionalize the surface of LCNPs using a layer-by-layer (LbL) self-assembly approach. To maximize their deep lung deposition, LF/CS-coated PEM-RES-LCNPs were then microencapsulated within various carriers to obtain inhalable nanocomposites via spray-drying techniques. The inhalable dry powder nanocomposites prepared using a mannitol-inulin-leucine (1:1:1 wt) mixture displayed superior in vitro aerosolization performance (2.72 μm of MMAD and 61.6% FPF), which ensured deep lung deposition. In lung cancer-bearing mice using urethane as a chemical carcinogen, the inhalable LF/CS-coated PEM-RES-LCNP nanocomposites showed superior antitumor activity as revealed by a considerable decrease of the average lung weight, reduced number and diameter of cancerous lung foci, decreased expression of VEGF-1, and increased expression of active caspase-3 as well as reduced Ki-67 expression compared to the spray-dried free PEM/RES powder mixture and positive control. Moreover, the in vivo fluorescence imaging confirmed successful lung deposition of the inhalable nanocomposites. Conclusively, the inhalable liquid crystalline nanocomposites elaborated in the current work could open new avenues for noninvasive lung cancer treatment.

Original languageEnglish
Pages (from-to)1030-1042
Number of pages13
JournalACS Biomaterials Science and Engineering
Volume6
Issue number2
DOIs
StatePublished - 10 02 2020

Bibliographical note

Publisher Copyright:
Copyright © 2020 American Chemical Society.

Keywords

  • chondroitin
  • inhalable nanocomposites
  • lactoferrin
  • layer-by-layer (LbL) coating
  • lung cancer
  • nanoparticulate liquid crystals

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