Hydrophobic ion pairing as a novel approach to co-axial electrospraying of peptide-PLGA particles

Electrospraying is a processing technique that has gained much interest to prepare polymeric particles. The technique operates at ambient temperature, thereby avoiding heat induced degradation of labile therapeutics (e. g. peptides and proteins). Exposure to organic solvents can be minimised by co-axial electrospraying through separation of core (aqueous) and shell (organic) solvents. However, aqueous solutions are often difficult to electrospray due to high surface tension. Immiscibility between the core-shell solvents creates a further process challenge. Herein, we describe for the first time the use of hydrophobic ion pairing (HIP) to encapsulate a polypeptide into polymeric particles prepared by co-axial electrospraying. Peptide ion pairs were prepared to incorporate a model peptide - teriparatide - into an organic solvent, permitting facile electrospraying while also protecting the peptide from denaturation. Teriparatide loaded PLGA particles were generated by electrospraying from aqueous or ethanolic peptide solutions (core). A PLGA solution in chloroform (with and without cosolvents) was employed as the shell solution. The aqueous core solution led to a teriparatide encapsulation efficiency of 79.2 f 19.8 %, which was not significantly different from the ethanolic core (57.1 f 14.5 %). When aqueous solutions were used the process lacked reproducibility, resulting in low process yields (61.3 f 4.0 %). In contrast, when an organic core was used a dry powder bed was achieved with a yield of 102.2 f 8.8 %. The peptide's integrity and biological functionality were retained after electrospraying as ion pairs, as evidenced in a cell-based PTH1 receptor binding assay.