Sustained release of peptides and proteins from polymeric nanocarriers produced by inverse Flash NanoPrecipitation
Peptide and protein therapeutics generally exhibit high potency and specificity and are increasingly important segments of the pharmaceutical market. However, their clinical applications are limited by rapid clearance and poor membrane permeability. Encapsulation of the peptide or protein into a nano-scale carrier can modify its pharmacokinetics and biodistribution.
Development of a nanoformulation process, Inverse Flash NanoPrecipitation (iFNP).
iFNP encapsulates hydrophilic drugs such as peptides and proteins into nanocarriers.
The two-step process produces tenfold higher drug loading than standard approaches.
Drug release is controlled by the properties of the block copolymer stabilizer.
Polymyxin B nanocarrier efficacy demonstrated in a murine lung infection model.
This might be employed to promote uptake in desired cell types or tissues, to limit systemic exposure, or to reduce the need for frequent injections. We have recently described inverse Flash NanoPrecipitation (iFNP), a scalable technique to encapsulate water-soluble therapeutics into polymeric nanocarriers, and have demonstrated improvements in therapeutic loading of an order of magnitude over comparable approaches. Here, we describe the formulation parameters that control release rates of encapsulated model therapeutics polymyxin B, lysozyme, and bovine serum albumin from nanocarriers produced using iFNP.
Using a neutropenic lung infection mouse model with a multi-drug resistant Acinetobacter baumannii clinical isolate, we demonstrate enhanced therapeutic effect and safety profile afforded by nanocarrier-encapsulated polymyxin B following pulmonary administration. The encapsulated formulation reduced toxicity observed at elevated doses and resulted in up to 2.7-log10 reduction in bacterial burden below that of unencapsulated polymyxin B. These results establish the promise of iFNP as a platform for nanocarrier delivery of water-soluble therapeutics.
Article information: Chester E. Markwalter, Robert F. Pagels, Ava Hejazi, Kurt D. Ristroph, Jiping Wang, Ke Chen, Jian Li, Robert K. Prud’homme. Sustained release of peptides and proteins from polymeric nanocarriers produced by inverse Flash NanoPrecipitation, Journal of Controlled Release, 2021. https://doi.org/10.1016/j.jconrel.2021.04.002.