Inhaled Ivermectin-Loaded Lipid Polymer Hybrid Nanoparticles: Development and Characterization

Author:

Kassaee Seyedeh Negin1ORCID,Ayoko Godwin A.2,Richard Derek3,Wang Tony4ORCID,Islam Nazrul156ORCID

Affiliation:

1. Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia

2. School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia

3. Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia

4. Central Analytical Research Facility, Institution for Future Environment, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia

5. Centre for Materials Science, Queensland University of Technology, Brisbane, QLD 4000, Australia

6. Centre for Immunology and Infection Control (CIIC), Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia

Abstract

Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr’s index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.

Publisher

MDPI AG

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