In vivo pharmacodynamics of lactoferrin-coupled lipid nanocarriers for lung carcinoma: intravenous versus powder for inhalation

Author:

Gaber Dina M.1,Nafee Noha2,Elzoghby Ahmed O.3,Helmy Maged W.4,Abdallah Osama Y.3

Affiliation:

1. Arab Academy for Science Technology and Maritime Transport College of Maritime Transport and Technology

2. College of Pharmacy: Kuwait University Faculty of Pharmacy

3. Alexandria University Faculty of Pharmacy

4. Damanhour University Faculty of Pharmacy

Abstract

Abstract Lung carcinoma characterized by high mortality rate and poor prognosis; the efficacy of drug delivery should improve drug exposure at the targeted site. this study aims at evaluating lactoferrin role as targeting ligand besides the administration route impact on tissue deposition and organ distribution. Lactoferrin (Lf)-coupled/uncoupled solid lipid nanoparticles (SLNs) were loaded with myricetin-phospholipid-complex (MYR-PH-CPX). Following physicochemical characterization, in-vitro antitumor activity and cellular uptake were investigated in A549-cell line. In-vivo deposition and biodistribution of fluorescently-labeled inhalable microparticles (with/without-Lf) were compared to intravenously administered fluorescently-labeled-SLNs (with/without-Lf) in mice. Lf-coupled-SLNs (98.59±0.47 nm), showed high entrapment efficiency (95.3±0.5%) and prolonged drug release. The in-vitro antitumor study showed reduction in IC50 for Lf-coupled-SLNs by ~2-and 3.5-fold relative to uncoupled-SLNs and MYR-PH-CPX, respectively confirming Lf role in enhancing antitumor activity by boosting cells internalization in shorter time. Furthermore, 3D-time laps confocal imaging showed that labeled-Lf-coupled-SLNs had a higher rate and extent of uptake in A549-cells compared to uncoupled-SLNs and free dye. In-vivo biodistribution proved that Lf enhanced pulmonary deposition of inhaled SLNs (~1.5 fold) and limited migration to the other organs within 6h relative to intravenous. Conclusively, local administration is superior due to less drug clearance resulting in lower toxicity accompanied by systemic application.

Publisher

Research Square Platform LLC

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