Recent emergence of biotherapeutic treatment such as protein or antibody administration led to novel challenges for the pharmaceutical industry such as thermal and chemical stability (pH-dependence, heat-induced denaturation, enzyme degradation) and control of drug release.1 To improve therapeutic protein release, mainly solvent-based entrapment processes were proposed especially through the formulation of liposomes1,2. In order to minimize solvent consumption, supercritical carbon dioxide (scCO2) technology was applied as alternative to biotherapeutic encapsulation as by the formulation of liposomes3 or by the entrapment of active molecule into polymeric excipients4. Among the supercritical process of polymeric encapsulation, the Particles from Gas Saturated Solutions (PGSS) offers the advantage to dispense with the use of organic solvents and to achieve yields approaching 100%. In this study, bovine serum albumin (BSA) well described in literature, was selected as a biomolecule model for its encapsulation through the PGSS process. Biodegradable polycaprolactone PCL as well as biodegradable/biocompatible polyester/polyether PCL blends (PCL/PLGA, PCL/PEG) were formulated for drug delivery applications and to investigate the influence of BSA/polymer ratio (1, 10 20 %). To prevent BSA thermal degradation, PGSS process was performed close to the human body temperature. High pressure differential scanning calorimetry and high-pressure visualization cell were coupled to select experimental conditions of pressure and temperature. The drug/polymer particles were compacted into implants prior to characterize by bicinchonic acid assay (BCA) the encapsulation yield and BSA loading and its release (up to 72h) in a PBS media. The obtained high particle recovery (close to 100 %), high drug precipitation yields (up to 81 %) and reproducible drug delivery profiles highlight the potential of PGSS process for sensitive biotherapeutic encapsulation.