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1.
Colloids Surf B Biointerfaces ; 188: 110750, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31884081

ABSTRACT

Upon inhalation, nanoparticles enter the lungs where the pulmonary surfactant forms the first point of contact and plays a pivotal role for the subsequent absorption into the body. This can lead to interactions that alter the biophysical function of the surfactant monolayer. Therefore, a reliable prediction of the interaction is desired. In this study, we compared the behaviour of an artificial surfactant model with that of a natural surfactant upon exposure to chitosan nanoparticles. To simulate the physiology of the lungs, the surfactant monolayers were placed at an air/aqueous interface of a Langmuir film balance. Based on the data obtained from the experiments, the chitosan nanoparticles first integrated into the monolayer of the natural surfactant and then interact strongly with its compounds thereby moving out of the monolayer. The topographic changes in the monolayer were determined by atomic force microscopy analysis. Using this technique, the nanoparticle localisation on the monolayer could be studied. No visible interaction was observed with the artificial surfactant from surface pressure-time isotherms and atomic force microscopy analysis. Incomplete miscibility lead to instability of the artificial surfactant which left behind a DPPC rich monolayer after nanoparticle interaction. It was not stable enough to see a possible interaction (i.e. change in surface pressure) with the nanoparticles directly. These results should help understand the interactions of lipids among themselves and with the nanoparticles. Furthermore, it should help generate an efficient artificial surfactant model and to understand the underlying mechanisms of the nanoparticle interaction with the monolayer.


Subject(s)
Lipids/chemistry , Nanoparticles/chemistry , Phospholipids/chemistry , Surface-Active Agents/chemistry , Particle Size , Surface Properties
2.
Eur J Pharm Sci ; 132: 63-71, 2019 Apr 30.
Article in English | MEDLINE | ID: mdl-30797026

ABSTRACT

Photodynamic therapy is amongst the most rapidly developing therapeutic strategies against cancer. However, most photosensitizers are administered intravenously with very few reports about pulmonary applications. To address this issue, an inhalable formulation consisting of nanoparticles loaded with photosensitizer (i.e. curcumin) was developed. The nanoparticles were prepared using nanoprecipitation method. Dynamic light scattering measurements of the curcumin loaded nanoparticles revealed a hydrodynamic diameter of 181.20 ±â€¯11.52 nm. In vitro irradiation experiments with human lung epithelial carcinoma cells (A549) showed a selective cellular toxicity of the nanoparticles upon activation using LED irradiating device. Moreover, curcumin nanoparticles exhibited a dose-dependent photocytotoxicity and the IC50 values of curcumin were directly dependent on the radiation fluence used. The nanoparticles were subsequently spray dried using mannitol as a stabilizer to produce Nano-in-Microparticles with appropriate aerodynamic properties for a sufficient deposition in the lungs. This was confirmed using the next generation impactor, which revealed a large fine particle fraction (64.94 ±â€¯3.47%) and a mass median aerodynamic diameter of 3.02 ±â€¯0.07 µm. Nano-in-Microparticles exhibited a good redispersibility and disintegrated into the original nanoparticles upon redispersion in aqueous medium. The Langmuir monolayer experiments revealed an excellent compatibility of the nanoparticles with the lung surfactant. Results from this study showed that the Nano-in-Microparticles are promising drug carriers for the photodynamic therapy of lung cancer.


Subject(s)
Curcumin/administration & dosage , Drug Carriers/administration & dosage , Nanoparticles/administration & dosage , Neoplasms/therapy , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , A549 Cells , Administration, Inhalation , Cell Culture Techniques , Cell Survival/drug effects , Cell Survival/radiation effects , Curcumin/pharmacology , Drug Compounding , Humans , Light , Photosensitizing Agents/pharmacology
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