Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

Table 3

Cell specific hepatic targeting of different drugs.

Type of cell/receptor	Drug	Further remarks	References
Hepatocytes and asialoglycoprotein; receptor	Iododeoxyuridine (IDU)	By isolating liver cells after injection of the iododeoxyuridine (IDU), it was concluded that hepatic uptake occurred mainly in parenchymal liver cells	[89]
Hepatocytes	Primaquine (PQ)	The prepared emulsion could be developed into a promising delivery system to target PQ into hepatocytes for vivax malaria therapy	[90]
Hepatocytes	5-Fluorouracil (5-FU)	The drug-loaded ZPs* could be efficiently targeted at the liver by intravenous delivery	[91]
Hepatic stellate cell (HSC)	Human serum albumin (HAS) modified with mannose6-phosphate (M6P)	M6P-modified albumins are taken up by HSC in fibrotic livers	[92]
Hepatic stellate cell; (HSC)	MicroRNAs	The study shows that there was direct target of miR-181b in HSC-T6 cell	[93]
Hepatic stellate cell; (HSC)	Antibody fragment	This antibody fragment may be an effective means to target therapeutics to human hepatic stellate cells	[94]
Hepatic carcinoma cell	Glycyrrhetinic acid-modified poly(ethylene glycol)-b-poly(c-benzyl L-glutamate) (GA-PEG-PBLG) micelles	In vitro cell uptake results indicated that the introduction of GA to the micelles significantly increased the affinity for human hepatic carcinoma	[95]
Hepatic carcinoma cells	Ribavirin nanoparticles	The nanoparticles had effective growth inhibitory activity in hepG2 human hepatoma cells	[96]
Hepatic carcinoma cell	Rhodamine B with lactose as ligand	The Lac-micelles will be an effective liver-targeting drug delivery system	[97]
Kupffer cell (nonparenchymal cells)	Cholesten-5-yloxy-𝑁-(4-((1-imino-2-b-D-thiomannosylethyl)amino)butyl)formamide (Man-C4-Chol) into small unilamellar liposomes consisting of cholesterol and distearoyl 3 phosphatidylcholine (DSPC)	The results suggest that Man liposomes are effective carriers for targeted delivery of bioactive compounds to liver NPC	[40]
Hepatic stellate cell; (HSC)	Pentoxifylline	PTX-neoglycoprotein mannose-6-phosphate-albumin (M6PHSA) employing a novel type of platinum linker, which allows sustained delivery of the drug to HSC in the fibrotic liver	[98]
Hepatocytes	Galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine (Gal-PEG-CHI-g-PEI)	Together, these results suggest that Gal-PEG-CHI-g-PEI, which has improved transfection efficiency and hepatocytes specificity both in vitro and in vivo, may be useful for gene therapy	[99]
Hepatocytes (asialoglycoprotein R)	Vitamin K5 and cytosine arabinoside using poly-L-glutamic acid and carboxymethyl dextran	Effective targeting to hepatocytes	[100]
Hepatic carcinoma cells	Ursodeoxycholic acid (UA) modified protein-lipid nanocomplex	The uptake of UA modified protein attached on the nanoparticles was higher in hepatic carcinoma cells (HepG2 and Bel 7402) than in normal liver cells	[101]
Hepatic carcinoma cell	Human telomerase reverse transcriptase with pegylated immuno-lipopolyplexes	The vector pApoAI-shTERT was able to cause liver-specific and hTERT target-specific cytotoxicity, and utilizing PILP to deliver pApoAI-shTERT is a promising strategy for liver-specific gene therapy	[102]
Nonparenchymal cells	Mannosylated superoxide dismutase; (SOD)	Increased delivery of SOD to nonparenchymal cell	[103]
Hepatocytes	Probucol liposomes	Hepatic uptake of liposomes should be mediated by asialoglycoprotein receptors being probucol incorporated in them	[104]
Endothelium cell	Paclitaxel (PTX)-loaded PEGylated PLGA-based nanoparticles grafted with RGD peptide	The targeting of anticancer drug to tumor endothelium by RGD-labeled NP is a promising approach	[105]
Hepatic stellate cells (HSC)	Cyclic Arg-Gly-Asp (RGD) peptides were combined with maleimide-[poly(ethylene glycol)]-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (MAL-PEG-DOPE) incorporated into stabilized liposomes	Targeted liposomes encapsulating HGF are a promising therapeutic modality in terms of promoting the remission of liver cirrhosis by promoting collagen fiber digestion, inhibiting collagen production and promoting apoptosis of 𝛼-SMA-positive cells in rats with cirrhosis	[106, 107]
Hepatocytes (asialoglycoprotein receptor)	Super paramagnetic iron oxide (SPIO) nanoparticles	These data underline the potential application of Gal-ASPIO as a targeted ligand for ASPGR-expressing cells in vivo	[107]
Hepatic carcinoma cell	Doxorubicin loaded super paramagnetic iron oxide nanoparticles	DOX is a promising candidate for treating liver cancer and monitoring the progress of the cancer using MRI	[108]

∗Zein nanoparticles.