Fluorescent PLGA Nanocarriers for Pulmonary Administration : Influence of the Surface Charge
Areny-Balagueró, Aina (Universitat Autònoma de Barcelona. Facultat de Medicina)
Mekseriwattana, Wid (School of Materials Science and Innovation, Faculty of Science, Mahidol University, Bangkok 10400, Thailand)
Camprubí-Rimblas, Marta (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias)
Stephany, Andrea (Institut de Ciència de Materials de Barcelona)
Roldan, Ariana (Institut de Ciència de Materials de Barcelona)
Solé-Porta, Anna (Institut de Ciència de Materials de Barcelona)
Artigas Raventós, Antoni (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Closa Autet, Daniel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Roig i Serra, Anna (Institut de Ciència de Materials de Barcelona)

Date:	2022
Abstract:	Nearly four million yearly deaths can be attributed to respiratory diseases, prompting a huge worldwide health emergency. Additionally, the COVID-19 pandemic's death toll has surpassed six million, significantly increasing respiratory disease morbidity and mortality rates. Despite recent advances, it is still challenging for many drugs to be homogeneously distributed throughout the lungs, and specifically to reach the lower respiratory tract with an accurate sustained dose and minimal systemic side effects. Engineered nanocarriers can provide increased therapeutic efficacy while lessening potential biochemical adverse reactions. Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, has attracted significant interest as an inhalable drug delivery system. However, the influence of the nanocarrier surface charge and its intratracheal instillation has not been addressed so far. In this study, we fabricated red fluorescent PLGA nanocapsules (NCs)-Cy5/PLGA-with either positive (Cy5/PLGA+) or negative surface charge (Cy5/PLGA-). We report here on their excellent colloidal stability in culture and biological media, and after cryo-storage. Their lack of cytotoxicity in two relevant lung cell types, even for concentrations as high as 10 mg/mL, is also reported. More importantly, differences in the NCs' cell uptake rates and internalization capacity were identified. The uptake of the anionic system was faster and in much higher amounts-10-fold and 2. 5-fold in macrophages and epithelial alveolar cells, respectively. The in vivo study demonstrated that anionic PLGA NCs were retained in all lung lobules after 1 h of being intratracheally instilled, and were found to accumulate in lung macrophages after 24 h, making those nanocarriers especially suitable as a pulmonary immunomodulatory delivery system with a marked translational character.
Grants:	Generalitat de Catalunya 2017SGR765
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Nanocarriers ; Lung ; PLGA ; Surface charge ; Intratracheal instillation ; Cell uptake
Published in:	Pharmaceutics, Vol. 14 (july 2022) , ISSN 1999-4923

DOI: 10.3390/pharmaceutics14071447
PMID: 35890341

17 p, 4.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles