Back to Search
Start Over
Pharmacological and toxicological assessment of innovative self-assembled polymeric micelles as powders for insulin pulmonary delivery.
- Source :
-
Nanomedicine (London, England) [Nanomedicine (Lond)] 2016 Sep; Vol. 11 (17), pp. 2305-17. Date of Electronic Publication: 2016 Aug 04. - Publication Year :
- 2016
-
Abstract
- Aim: Explore the use of polymeric micelles in the development of powders intended for pulmonary delivery of biopharmaceuticals, using insulin as a model protein.<br />Materials & Methods: Formulations were assessed in vitro for aerosolization properties and in vivo for efficacy and safety using a streptozotocin-induced diabetic rat model.<br />Results: Powders presented good aerosolization properties like fine particle fraction superior to 40% and a mass median aerodynamic diameter inferior of 6 μm. 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.<br />Conclusion: Developed powders showed promising safety and efficacy characteristics for the systemic delivery of insulin by pulmonary administration.
- Subjects :
- Administration, Inhalation
Animals
Diabetes Mellitus, Experimental blood
Drug Carriers chemistry
Drug Delivery Systems
Hypoglycemic Agents blood
Hypoglycemic Agents therapeutic use
Insulin blood
Insulin therapeutic use
Lung drug effects
Lung metabolism
Male
Polymers chemistry
Powders
Rats
Rats, Wistar
Diabetes Mellitus, Experimental drug therapy
Drug Carriers toxicity
Hypoglycemic Agents administration & dosage
Insulin administration & dosage
Micelles
Polymers toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1748-6963
- Volume :
- 11
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Nanomedicine (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 27487859
- Full Text :
- https://doi.org/10.2217/nnm-2016-0045