Highly Loaded Nanoparticulate Formulation of Progesterone for Emergency Traumatic Brain Injury Treatment

Abstract

Background: Progesterone (PG), a promising therapeutic for treating traumatic brain injury, has been difficult to formulate into a high-dose/low-volume form for emergency intravenous administration due to its hydrophobicity and crystallinity. Results: This work demonstrates the use of Flash NanoPrecipitation to produce 300-nm PG-loaded polymeric nanoparticles with approximately 24 wt% drug loading using only components that are classified by the US FDA as generally recognized as safe. Approximately 80% of the encapsulated PG is in dissolved, rather than crystalline form. For prolonged stability, the nanoparticles are freeze–dried with Pluronic F68 and can be reproducibly reconstituted by hand agitation for 1 min without particle aggregation to produce injectable formulations with approximately 30-mg/ml PG, which is more than ten-times higher than has been previously reported. Conclusion: This formulation can allow for administration of therapeutically viable concentrations of PG, which has been impossible with all previously reported nanoparticulate formulations because of low drug loadings and concentrations.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Aknowledgements

The authors would like to thank H Bowman of Evonik Birmingham Laboratories for the synthesis of the poly(ethylene glycol)-block-poly(D,L-lactide) copolymers and continued support.

Financial & competing interests disclosure

This work was made possible through support from the National Science Foundation through the NIRT ‘Nanoscale Interdisciplinary Research Teams‘ (CTS-0506966) and the Helen Shipley Hunt Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.