4.7 Article

Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 69, Issue -, Pages 267-276

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2014.12.007

Keywords

rhINF-alpha-2b; Aquasomes; Trehalose; Cellobiose; Pyridoxal-5-phosphate; Phospholipid-PEG(2000); Cytotoxicity

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Purpose: In present investigation, recombinant human interferon-alpha-2b (rhINF-alpha-2b) loaded aquasomes were prepared, optimized and overlaid with PEGylated phospholipid to offer prolong release and high therapeutic index against ovarian cancer, SKOV3 cells. Methods and results: Central Composite Design (CCD) and Response Surface Methodology (RSM) were employed to calculate the optimized conditions, 1: 3 core to coat ratio, sonication power of 12.5 W and time of about 55 min for preparation of aquasomes. Consequently, rhINF-alpha-2b-Py-5-P-Aq. somes exhibited higher protein loading capacity and retained structural conformations of rhINF-alpha-2b, as compared to rhINF-alpha-2b-Cellob-Aq. somes, rhINF-alpha-2b-Tre-Aq. somes and rhINF-alpha-2b-Core (CaHPO4). Further, optimized rhINF-alpha-2b-Py-5-P-Aq. somes was superimposed with phospholipid-PEG2000 to prolong the release pattern of rhINF-alpha-2b from aquasomes. The rhINF-alpha-2b-core (CaHPO4) released 97.3% of protein in 1 h, while 95.3% of rhINF-alpha-2b was released by rhINF-alpha-2b-Tre-Aq. somes in 4 h. Concurrently, rhINF-alpha-2b-Cellob-Aq. somes and rhINF-alpha-2b-Py-5-P-Aq. somes released 96.2% and 97.8% of rhINF-alpha-2b respectively in 6 and 8 h. Ultimately, rhINF-alpha-2b-Py-5-P-Aq. somes-P-PEG2000 displayed evidence of its prolonged release pattern and released 98.1% of rhINF-alpha-2b in 336 h. FT-IR and XRD substantiated the involvement of vigorous intermolecular hydrogen bonding and amorphous geometry in rhINF-alpha-2b-Py-5-P-Aq. somes. In last, rhINF-alpha-2b-Py-5-P-Aq. somes-P-PEG(2000) exhibited the similar to 4.55, 1.92, 2.3, 2.8, and 3.84 fold reductions in IC50 as compared to free rhINF-alpha-2b, rhINF-alpha-2b-Py-5-PAq. somes, rhINF-alpha-2b-Cellob-Aq. somes, rhINF-alpha-2b-Tre-Aq. somes and rhINF-alpha-2b-Core (CaHPO4), respectively. Conclusion: Therefore, rhINF-alpha-2b-Py-5-P-Aq. somes-P-PEG(2000) warrant further in depth in vitro and in vivo antitumor study to scale up the technology for clinical intervention. (C) 2014 Elsevier Masson SAS. All rights reserved.

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