Fluorescent PLGA Nanocarriers for Pulmonary Administration: Influence of the Surface Charge
Issued Date
2022-07-01
Resource Type
eISSN
19994923
Scopus ID
2-s2.0-85137296964
Journal Title
Pharmaceutics
Volume
14
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pharmaceutics Vol.14 No.7 (2022)
Suggested Citation
Areny-Balagueró A., Mekseriwattana W., Camprubí-Rimblas M., Stephany A., Roldan A., Solé-Porta A., Artigas A., Closa D., Roig A. Fluorescent PLGA Nanocarriers for Pulmonary Administration: Influence of the Surface Charge. Pharmaceutics Vol.14 No.7 (2022). doi:10.3390/pharmaceutics14071447 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86846
Title
Fluorescent PLGA Nanocarriers for Pulmonary Administration: Influence of the Surface Charge
Author's Affiliation
Institut d’Investigació i Innovació Parc Taulí (I3PT)
CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB)
Universitat Autònoma de Barcelona
Mahidol University
CSIC - Instituto de Investigaciones Biomedicas de Barcelona (IIBB)
Instituto de Salud Carlos III
Corporació Sanitària i Universitària Parc Taulí
CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB)
Universitat Autònoma de Barcelona
Mahidol University
CSIC - Instituto de Investigaciones Biomedicas de Barcelona (IIBB)
Instituto de Salud Carlos III
Corporació Sanitària i Universitària Parc Taulí
Other Contributor(s)
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.