Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug

• Main Authors: Amolnat Tunsirikongkon (Author), Yong-Chul Pyo (Author), Dong-Hyun Kim (Author), Sang-Eun Lee (Author), Jeong-Sook Park (Author)
• Format: Book
• Published: MDPI AG, 2019-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1999-4923; 10.3390/pharmaceutics11060272
• Keywords: poly-<span style="font-variant: small-caps">l</span>-arginine; DSPE-PEG; cationic proliposome; cellular association; cytotoxicity; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 11, Iss 6, p 272 (2019)

The purpose of this study was to develop an oral proliposomal powder of protein using poly-<span style="font-variant: small-caps;">l</span>-arginine-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (PLD) for enhancing cellular association upon reconstitution and to compare its effects with a non-grafted and PEGylated formulation. Cationic proliposome (CATL), PLD-grafted CATL (PLD-CATL), PEGylated CATL (PEG CATL), and PLD grafted-PEG CATL (PLD-PEG CATL) were prepared and compared. Successful conjugation between poly-<span style="font-variant: small-caps;">l</span>-arginine and DSPE-PEG was confirmed by ¹H NMR and FT-IR. PLD was successfully grafted onto the proliposomal powder during the slurry process. Although reconstituted liposomal sizes of CATL and PLD-CATL were increased by agglomeration, PEGylation reduced the agglomeration and increased the encapsulation. The viabilities of cells treated with both CATL and PLD-CATL formulations were low but increased following PEGylation. With regard to cellular association, PLD-CATL enhanced cellular association/uptake more rapidly than did CATL. Upon PEGylation, PEG CATL showed a lower level of cellular association/uptake compared with CATL while PLD-PEG CATL did not exhibit the rapid cellular association/uptake as seen with PLD-CATL. However, PLD-PEG CATL still enhanced the higher cellular association/uptake than PEG CATL did without PLD. In conclusion, proliposomes with PLD could accelerate cellular association/uptake but also caused high cellular toxicity. PEGylation reduced cellular toxicity and also changed the cellular association pattern of the PLD formulation.