Pharmacological and toxicological assessment of innovative self-assembled polymeric micelles as powders for insulin pulmonary delivery

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Andrade, F (Author) Other; Fonte, P (Author) Other; Costa, A (Author) Other; Reis, CC (Author) Other; Nunes, R (Author) Other; Almeida, A (Author) Other; Ferreira, DC (Author) FFUP; Oliva, M (Author) Other; Sarmento, B (Author) Other

Journal

Title: Nanomedicine

Vol. 11

Pages: 2305-2317

ISSN: 1743-5889

Publisher: Future Medicine Ltd.

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 21 Citations

Other information

Authenticus ID: P-00K-V01

DOI: 10.2217/nnm-2016-0045

Abstract (EN): Aim: Explore the use of polymeric micelles in the development of powders intended for pulmonary delivery of biopharmaceuticals, using insulin as a model protein. Materials & methods: Formulations were assessed in vitro for aerosolization properties and in vivo for efficacy and safety using a streptozotocin-induced diabetic rat model. Results: Powders presented good aerosolization properties like fine particle fraction superior to 40% and a mass median aerodynamic diameter inferior of 6 mu m. Endotracheally instilled powders have shown a faster onset of action than subcutaneous administration of insulin at a dose of 10 IU/kg, with pharmacological availabilities up to 32.5% of those achieved by subcutaneous route. Additionally, micelles improved the hypoglycemic effect of insulin. Bronchoalveolar lavage screening for toxicity markers (e.g., lactate dehydrogenase, cytokines) revealed no signs of lung inflammation and cytotoxicity 14 days postadministration. Conclusion: Developed powders showed promising safety and efficacy characteristics for the systemic delivery of insulin by pulmonary administration.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13