Poly (Ethylene Glycol)-<b><i>Block</i></b>-Brush Poly (L-Lysine) Copolymer as an Efficient Nanocarrier for Human Hepatocyte Growth Factor with Enhanced Bioavailability and Anti-Ischemia Reperfusion Injury Efficacy

Abstract

Background/Aims: The aim of this study was to assess the effect of human hepatocyte growth factor (hHGF)-loaded poly (ethylene glycol)-b-brush poly (l-lysine) (PEG-b-P(ELG-g-PLL)) copolymer on ischemia/reperfusion (I/R) injury to different organs. Methods: The isoelectric point (pI) of hHGF is 5.5, and hHGF combined with PEG-b-P(ELG-g-PLL) copolymer via electrostatic interactions at pH 7.4. The synthesized PEG-b-P(ELG-g-PLL) copolymer was analyzed using ¹H nuclear magnetic resonance (¹H NMR) and gel permeation chromatography (GPC). The hHGF/PEG-b-P(ELG-g-PLL) complex was evaluated using a nanoparticle size instrument and transmission electron microscopy (TEM). In addition, vivo performance of hHGF/PEG-b-P(ELG-g-PLL) complex was evaluated using plasma hHGF concentration and different organs ischemia reperfusion injury in rats. Results: An in vitro investigation showed that PEG-b-P(ELG-g-PLL) could serve as a potential hHGF nanocarrier with efficient encapsulation and sustained release. An additional in vivo investigation revealed that the hHGF/PEG-b-P(ELG-g-PLL) complex could prolong increases in plasma hHGF concentration and protect different organs (the brain, heart and kidney) against I/R injury. Conclusion: Poly (ethylene glycol)-block-brush poly (l-lysine) copolymer as an efficient nanocarrier for human hepatocyte growth factor with enhanced bioavailability and anti-ischemia reperfusion injury efficacy.

In vitro/vivo drug release and anti-diabetic cardiomyopathy properties of curcumin/PBLG-PEG-PBLG nanoparticles

“…For a detailed measurement of cytotoxicity by the cell culture and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (H9C2 cells were selected) of P and curcumin/P, please refer to our previous studies. [39][40][41][42][43]…”

Ischemia Reperfusion Injury: Opportunities for Nanoparticles

“…PLL–PEG–PLL exenatide complexes preserved myocardial function via attenuating oxidative stress and inflammation . Human hepatocyte growth factor-loaded copolymer micelles showed enhanced plasma concentration and bioavailability against multiple organ IR injury …”

Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer

“…PEG-b-(PELG-g-(PZLL-r-PLL)) was synthesized according to our previous method. [29][30][31][32][33] Briefly, PEG-b-PBLG was first synthesized by the ring-opening polymerization of BLG-NCA with PEG-NH 2 in the presence of DMF. PEG-b-PELG was then obtained by the aminolysis with ethylenediamine from PEG-b-PBLG.…”

“…The synthesis of the PEG-b-(PELG-g-(PZLL-r-PLL)) polymers as described previously. [29][30][31][32][33] The negatively charged LK (the isoelectric point is 4.61) combines with a positively charged PLL brush block through electrostatic interactions, and hydrophobic PTX combines with PZLL through hydrophobic interaction at pH 7.4. The loaded LK and PTX ensure sustained release, which can improve the protective effect and bioactivity of each drug.…”