(410a) Formulating Biologics in Polymeric Nanoparticles: New Methods to Overcome Manufacturing Barriers

Nanoscale polymeric vehicles can protect biologics such as peptides and proteins from clearance and produce a sustained release profile.1 The double emulsion process to form polymeric microparticles and nanoparticles is a commonly employed formulation technique but has well-documented trade-offs.2 This results in processes that are not economically viable because significant therapeutic quantities are lost as unencapsulated material. To achieve the same therapeutic dose with a low-loading formulation requires large excipient amounts and possibly high-volume injections.

We have developed a process that addresses these shortcomings by replacing the primary emulsion with an “inverse nanoparticle” 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, 24–37.

(2) Pagels, R. F.; Prud’homme, R. K. Polymeric Nanoparticles and Microparticles for the Delivery of Peptides, Biologics, and Soluble Therapeutics. J. Control. Release 2015, 219, 519–535.

(3) Markwalter, C. E.; Prud’homme, R. K. Inverse Flash NanoPrecipitation for Biologics Encapsulation: Understanding Process Losses via an Extraction Protocol; 2017; pp 275–296.

(4) Pagels, R. F.; Prud’homme, R. K. Inverse Flash NanoPrecipitation for Biologics Encapsulation: Nanoparticle Formation and Ionic Stabilization in Organic Solvents; 2017; pp 249–274.