A Novel Non-Aqueous Emulsification Platform to Fabricate Polymeric Microspheres for Sustained Delivery of Biologics

Polymeric microspheres (MS) have been developed with moderate success using aqueous emulsification (AqE) for small molecules and peptides with a few approved products. AqE faces a challenge to achieve optimal encapsulation of large hydrophilic molecules such as proteins/mAbs. To overcome this, a novel non-aqueous emulsification platform, "FluoriPack" (FP), was developed. FP is a solid/hydrocarbon/fluorocarbon (S/H/F) platform that enables high biologic loading within MS, with minimal impact on biologic integrity.

To develop MS using FP, a model protein was encapsulated in polyorthoester (POE) MS via non-aqueous emulsification. The continuous phase was Fluorinert™ FC-40 containing a fluorosurfactant (PicoSurf™ 1). Protein loaded MS were evaluated for morphology, PSD, % loading & in-vitro release (IVR), accelerated stability testing, and toxicity of blank microspheres. Encapsulated protein released from MS were evaluated for integrity and potency.

Preliminary evaluation indicates that MS prepared via FP (FP-MS) were superior to AqE-MS, indicated by the surface morphology (non-porous versus porous), encapsulation (> 60% versus < 10%), and burst release (< 40% versus > 75%). FP-MS had a mean diameter of ~ 40 µm and were stable over 1-month at accelerated conditions. No toxicity was observed in mammalian cells with > 80% viability post FP-MS treatment. The biologic retained integrity post-encapsulation with minimal aggregation (Δ 1.1%) and high potency (> 80%). In vitro release evaluation revealed a sustained release of biologic over 9 days (~ 8% every 24 h).

MS prepared using FluoriPack achieved the desired quality attributes, enabling it to be a promising tool for sustained delivery of biologics.