Universitas Indonesia Conferences, Asian Federation for Pharmaceutical Sciences (AFPS) 2019

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Surface Modification of PEGylated Proliposome Formulation to Improve Cellular Association of Protein Drug
Yong-Chul Pyo, Amolnat Tunsirikongkon, Sang-Eun Lee, Dong-Hyun Kim, Phuong Tran, Chang-Seon Myung, JEONG-SOOK PARK

Last modified: 2019-06-15


Background: Low bioavailability of protein drug upon oral administration has long been recognized as an immense challenge for oral protein delivery. Objective: This study aimed to develop an oral proliposomal powder of protein using poly-L-arginine-conjugated DSPE-PEG (PLD) for enhancing cellular association upon reconstitution and to compare its effects with a non-grafted and PEGylated formulation. Materials and Methods: Cationic proliposome (CATL), PLD-grafted CATL (PLD-CATL), PEGylated CATL (PEG CATL), and PLD grafted-PEG CATL (PLD-PEG CATL) were prepared and compared. Conjugation between poly-L-arginine and DSPE-PEG was confirmed by 1H NMR and FT-IR. Results: PLD was successfully grafted onto the proliposomal powder during the slurry process. Although reconstituted particle 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 more rapidly than did CATL. Upon PEGylation, PEG-CATL showed a lower level of cellular association compared with CATL while PLD-PEG CATL did not exhibit the rapid cellular association as seen with PLD-CATL. However, PLD-PEG CATL still enhanced the higher cellular association than did PEG-CATL without PLD. Conclusion: Based on these results, proliposomes with PLD could accelerate cellular association but also caused high cellular toxicity. PEGylation reduced cellular toxicity and also changed the cellular association pattern of the PLD formulation.