Ameliorative Effect of Curcumin-Encapsulated Hyaluronic Acid–PLA Nanoparticles on Thioacetamide-Induced Murine Hepatic Fibrosis

Abstract

In this study, we developed curcumin-encapsulated hyaluronic acid–polylactide nanoparticles (CEHPNPs) to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA) receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs) rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs. HA and polylactide (PLA) were crosslinked by adipic acid dihydrazide (ADH). The synthesis of HA–PLA was monitored by Fourier-transform infrared (FTIR) and Nuclear Magnetic Resonance (NMR). The average particle size was approximately 60–70 nm as determined by dynamic light scattering (DLS) and scanning electron microscope (SEM). Zeta potential was around −30 mV, which suggested a good stability of the particles. This drug delivery system induced significant aHSC cell death without affecting quiescent HSCs, hepatic epithelial, and parenchymal cells. This system reduced drug dosage without sacrificing therapeutic efficacy. The cytotoxicity IC50 (inhibitory concentration at 50%) value of CEHPNPs was approximately 1/30 to that of the free drug treated group in vitro. Additionally, the therapeutic effects of CEHPNPs were as effective as the group treated with the same curcumin dose intensity in vivo. CEHPNPs significantly reduced serum aspartate transaminase/alanine transaminase (ALT/AST) significantly, and attenuated tissue collagen production and cell proliferation as revealed by liver biopsy. Conclusively, the advantages of superior biosafety and satisfactory therapeutic effect mean that CEHPNPs hold great potential for treating hepatic fibrosis.

Macrophage repolarization using CD44-targeting hyaluronic acid–polylactide nanoparticles containing curcumin

“…Also, FT-IR spectrum shows bands at 2800 $ 2900 cm À1 for stretching in the C-H of PLA. These peaks of FTIR were similar to found in literature [37,38]. Shifting the peaks of HA amide bond from 1614 to 1648 cm À1 generate HA-ADH amide bond, which demonstrated the bonding of HA to ADH.…”

“…Usage of PVA, as a stabilizing agent, reduce drug leakage from NPs and improve drug-loading efficiency. Also, applying O/W (acetone/ddH2O) ratio 1:4 can increase drug-loading efficiency [37].…”

Hepato therapeutic Efficacy of Native Curcumim and Nano –curcumin : A Novel Therapy Against Hyperthyroidism Induced Liver Oxidative and Inflammatory Damage in Rats

“…Similarly, enhanced antiangiogenic effects of curcumin including inhibition of HUVEC proliferation, migration, invasion, and tube formation were noticed in human liver cancer SMMC 7721 cells treated with curcumin encapsulated in pHsensitive polymeric nanoparticles [22]. Curcumin encapsulated hyaluronic acidpolylactide nanoparticles significantly reduced serum aspartate transaminase and alanine transaminase, attenuated tissue collagen production and cell proliferation and ameliorated thioacetamide-induced murine hepatic fibrosis [23]. In line, vesicular and nanoparticulate delivery of curcumin was able to attenuate inflammation, oxidative stress and protect carbon tetrachloride induced hepatocellular damage in a rat model [24].…”

Multi-Drug/Gene NASH Therapy Delivery and Selective Hyperspectral NIR Imaging Using Chirality-Sorted Single-Walled Carbon Nanotubes

“…In this progression, activated hepatic stellate cells (aHSCs) responsible for fibrosis development are often described as pericytes for angiogenesis and vascular remodeling in the liver [43]. Fibrosis mediated by HSCs is associated with the effects of inflammation, as multiple inflammatory cytokines are known to elicit further activation of HSCs [44]. Although the entire process is not fully understood, fibrotic cytokine release (i.e., TGF-β, sonic hedgehog, and TNF-α) in the course of NASH is believed to contribute to the progression of the latter through the fibrotic stage and cirrhosis to HCC [28].…”