Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin

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• 作者：Fernanda Andrade ; MSc^a ; ^b ; ^c ; ^{fersilandrade@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; José ; das Neves ; PhD^d ; ^e ; ^f ; Petra Gener ; PhD^g ; ^h ; Simó ; Schwartz Jr. ; PhD^g ; ^h ; Domingos Ferreira ; PhD^a ; Mireia Oliva ; PhD^b ; ^c ; ^h ; Bruno Sarmento ; PhD^d ; ^e ; ^f ; ^{bruno.sarmento@ineb.up.pt" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Polymeric micelles ; Inhalation ; Cytotoxicity ; Permeability ; Phagocytosis ; Protein delivery
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：11
• 期：7
• 页码：1621-1631
• 全文大小：1561 K

文摘

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®, Pluronic® F68, Pluronic® F108 and Pluronic® 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 渭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® 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.