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Open AccessArticle

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

College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea
Division of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Rangsit Center, Pathumthani 12120, Thailand
Author to whom correspondence should be addressed.
Both authors contributed equally to this work.
Pharmaceutics 2019, 11(6), 272;
Received: 14 May 2019 / Revised: 4 June 2019 / Accepted: 7 June 2019 / Published: 11 June 2019
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
The purpose of this study was to develop an oral proliposomal powder of protein using poly-l-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-l-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. View Full-Text
Keywords: poly-l-arginine; DSPE-PEG; cationic proliposome; cellular association; cytotoxicity poly-l-arginine; DSPE-PEG; cationic proliposome; cellular association; cytotoxicity
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MDPI and ACS Style

Tunsirikongkon, A.; Pyo, Y.-C.; Kim, D.-H.; Lee, S.-E.; Park, J.-S. Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug. Pharmaceutics 2019, 11, 272.

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