(410a) Formulating Biologics in Polymeric Nanoparticles: New Methods to Overcome Manufacturing Barriers
- Conference: AIChE Annual Meeting
- Year: 2019
- Proceeding: 2019 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Tuesday, November 12, 2019 - 3:30pm-3:51pm
We have developed a process that addresses these shortcomings by replacing the primary emulsion with an âinverse nanoparticleâ containing the biologic. We employ inverse Flash NanoPrecipitation (iFNP) to produce these polymeric nanoparticles encapsulating a biologic at high loading (>50%).3,4 These inverse nanoparticles reduce process losses during production of the second emulsion due to the presence of a hydrophobic polymer shell around each biologic core. Alternatively, we have developed a process to introduce a dense PEG coating on the inverse nanoparticles to produce long-circulating water-dispersible particles structurally analogous to polymersomes or vesicles.
We detail the methods employed in forming these particulate delivery systems for sustained release applications. The loadings and encapsulation efficiencies (EE) achieved are in many cases an order of magnitude better than existing techniques. We will report approaches for tuning releases profiles and describe potential applications of the technology. The table below highlights process metrics for a range of biologics encapsulated in coated nanoparticles formed by iFNP.
(1) Yu, M.; Wu, J.; Shi, J.; Farokhzad, O. C. Nanotechnology for Protein Delivery: Overview and Perspectives. J. Control. Release 2016, 240, 24â37.
(2) Pagels, R. F.; Prudâhomme, R. K. Polymeric Nanoparticles and Microparticles for the Delivery of Peptides, Biologics, and Soluble Therapeutics. J. Control. Release 2015, 219, 519â535.
(3) Markwalter, C. E.; Prudâhomme, R. K. Inverse Flash NanoPrecipitation for Biologics Encapsulation: Understanding Process Losses via an Extraction Protocol; 2017; pp 275â296.
(4) Pagels, R. F.; Prudâhomme, R. K. Inverse Flash NanoPrecipitation for Biologics Encapsulation: Nanoparticle Formation and Ionic Stabilization in Organic Solvents; 2017; pp 249â274.