Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro–in vivo aerosol performance

Patil-Gadhe, Arpana; Kyadarkunte, Abhay; Patole, Milind; Pokharkar, Varsha

doi:10.1016/j.ejpb.2014.07.007

Cited by 84Inhalation and Respiratory Drug DeliveryNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems

Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro–in vivo aerosol performance

Patil-Gadhe, Arpana, Kyadarkunte, Abhay, Patole, Milind, Pokharkar, Varsha·2014·European Journal of Pharmaceutics and Biopharmaceutics

DOI 10.1016/j.ejpb.2014.07.007

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Abstract

The aim of the present study was to establish the potential of montelukast loaded nanostructured lipid carrier (MNLC) for pulmonary application. The formulated nanoparticles were evaluated in vitro for aerodynamic characterization and in vivo for pulmokinetics in Wistar rats. The in vitro cytotoxicity was performed on A549 cell line and compared with montelukast-aqueous solution. MNLC was prepared with montelukast (0.2%), Precirol ATO5 (solid lipid), and Capryol-90 (liquid lipid) in the ratio of 7:3 using melt-emulsification-homogenization method. dl-Pyrrolidonecarboxylic acid salt of l-cocyl arginine ethyl ester (CAE), a biodegradable surfactant in the concentration of 1% was used to stabilize the nanoparticles. The particle size and encapsulation efficiency (EE) were 184.6 ± 2.7 nm and >95%, respectively. MNLC-Dry powder for inhalation (DPI) was prepared by lyophilization using 3% mannitol as cryoprotectant and carrier. MNLC-DPI was evaluated for flow, crystallographic and thermal properties. Mass median diameters (MMD) and density for MNLC-DPI were found to be 15.1 ± 1.4 μm and 0.051 ± 0.002 g/cc, respectively. In vitro aerosol performance study indicated more than 95% of the emitted dose (ED) at both the flow rates studied. Mass median aerodynamic diameters (MMAD) of 3.24 ± 0.67 μm with 69.98 ± 1.9% fine particle fraction (FPF) were obtained at 30 L/min flow rate, whereas at 60 L/min MMAD and FPF were found to be 2.83 ± 0.46 μm and 90.22 ± 2.6%, respectively. In vitro cytotoxicity study on A549 cells revealed higher safety of MNLC than pure drug. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 11.76 for MNLC as compared to montelukast-aqueous solution. Thus, the results of the study demonstrated the potential of montelukast lipidic nanoparticulate formulation to improve the efficacy with reduced toxicity leading to better performance of drug as MNLC-DPI for inhalation use.

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Inhalable montelukast-loaded nanostructured lipid carriers improved systemic bioavailability (12-fold) and therapeutic outcomes compared to montelukast aqueous solutions.
“Inhalable montelukast-loaded nanostructured lipid carriers have been found to improve systemic bioavailability (12-fold) and eventual therapeutic outcomes compared to those of montelukast aqueous solutions.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [173]
Inhalable drugs reduce dosing frequency, and bypassing first pass hepatic metabolism reduces hepatocellular toxicity.
“Inhalable drugs reduce dosing frequency, and bypassing the first pass hepatic metabolism reduces hepatocellular toxicity.173,174”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [173]

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Authors: Patil-Gadhe, A., Kyadarkunte, A., Patole, M., & Pokharkar, V.
Affiliations: National Centre for Cell Science (IN)
Bharati Vidyapeeth (Deemed to be University) (IN)
Corresponding author: Pokharkar, Varsha
ORCID: Pokharkar, Varsha
Venue: European Journal of Pharmaceutics and Biopharmaceutics
Publisher: Elsevier BV
Published: 2014-09
Volume: 88
Issue: 1
Pages: 169-177
ISSN: 0939-6411 (ISSN-L)
DOI: 10.1016/j.ejpb.2014.07.007
OpenAlex: W1983470373
Cited by: 84
References: 64
Citations by year: 2026: 2 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 12 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 3 · 2016: 5 · 2015: 4
FWCI: 3.20
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: montelukast, nanostructured lipid carriers, pulmonary drug delivery, dry powder inhaler, aerosol performance, fine particle fraction, pulmonary pharmacokinetics, lung targeting, cytotoxicity, A549 cells, freeze-drying, biodegradable surfactants, encapsulation efficiency, solid lipid nanoparticles, drug bioavailability
MeSH terms: Acetates, Administration, Inhalation, Aerosols, Animals, Cyclopropanes, Diglycerides, Humans, Lipids, Lung, Male, Particle Size, Polymers, Powders, Propylene Glycols, Quinolines, Sulfides, Drug Delivery Systems, Rats, Wistar, Cell Line, Tumor, Rats, Nanoparticles, Dry Powder Inhalers

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Montelukast-loaded nanostructured lipid carriers: Part II Pulmonary drug delivery and in vitro–in vivo aerosol performance

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