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Inhalable Lactoferrin/Chondroitin-Functionalized Monoolein Nanocomposites for Localized Lung Cancer Targeting
- Source :
- ACS biomaterials scienceengineering. 6(2)
- Publication Year :
- 2021
-
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.
- Subjects :
- Lung Neoplasms
0206 medical engineering
Biomedical Engineering
02 engineering and technology
Glycerides
Nanocomposites
Biomaterials
chemistry.chemical_compound
Mice
medicine
Chondroitin
Animals
Chondroitin sulfate
Lung cancer
Lung
Aerosolization
biology
Lactoferrin
021001 nanoscience & nanotechnology
medicine.disease
020601 biomedical engineering
Pemetrexed
chemistry
Drug delivery
Cancer research
biology.protein
Nanocarriers
0210 nano-technology
medicine.drug
Subjects
Details
- ISSN :
- 23739878
- Volume :
- 6
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- ACS biomaterials scienceengineering
- Accession number :
- edsair.doi.dedup.....bf1c9c1f67ff737b9a9517dd8c36a84d