Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug
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 associat...
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| Main Authors: | , , , , |
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| Format: | Book |
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MDPI AG,
2019-06-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | 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 <sup>1</sup>H 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. |
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| Item Description: | 1999-4923 10.3390/pharmaceutics11060272 |