Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 11, Issue 7, Pages 1621-1631Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2015.05.006
Keywords
Polymeric micelles; Inhalation; Cytotoxicity; Permeability; Phagocytosis; Protein delivery
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [SFRH/BD/73062/2010]
- European Regional Development Fund (ERDF) through the Programa Operacional Factores de Competitividade-COMPETE
- FCT [PEst-C/SAU/LA0002/2013]
- North Portugal Regional Operational Programme (ON.2-O Novo Norte) under the National Strategic Reference Framework (NSRF) [SAESCTN-PIICDT/2011]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/73062/2010] Funding Source: FCT
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Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus (R), Pluronic (R) F68, Pluronic (R) F108 and Pluronic (R) F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 mu m) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic (R) F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. From the Clinical Editor: The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies. (C) 2015 Elsevier Inc. All rights reserved.
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