Protection of Protein Drugs by Self-Emulsified Nanoemulsion Against Proteolysis

The present study aimed to develop a self-emulsified nanoemulsion for salmon calcitonin (sCT) for noninvasive delivery. Hydrophobic ion pairing method was used to form hydrophobic complex of sCT with 4 counter ions (oleate, deoxycholate, docusate and tripolyphosphate). The partition coefficient and dissociation of the complexes in water of various pH were investigated. The complex-loaded nano emulsions were characterized for droplet size, leakage of sCT from the droplets, and protection of sCT from enzymatic degradation. The results show that all the counter ions could form complexes with sCT with a complexation efficiency about 95% at pH 8.0. The complexes significantly increased the partition coefficient of sCT. The dissociation of the complexes in water was pH-dependent. At pH 6.8 and 7.4, the dissociation was negligible. At pH 1.0, the dissociation was 71%, 8%, 37% and 50% for sCT-polyphosphate, sCT-docusate, sCT-oleate and sCT-deoxycholate, respectively. The developed nanoemulsions had a size in the range of 27-62 nm. The leakage of sCT from the nanodroplets into the aqueous phase depended on the lipophilicity of the counter ions: 60%, 56%, and 24% leakage for sCT-docusate, sCT-oleate and sCT deoxycholate, respectively. The nanoemulsion protected sCT from enzyme degradation when loaded inside the droplets, but not the leaked sCT. (c) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.