Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

Table 2

Different ligand-based liver targeting approaches and conclusions.

Drug	Ligand	Conclusion	References
Doxorubicin	Galactosamine	GAL-DOX-AN is more effective in killing HepG2 cell than DOX-AN	[75]
Sugar charge-modified albumins	Lactose, mannose	Study demonstrates that cell-specific delivery of sugar- and charge-modified albumins in fibrotic livers is possible by coupling drugs to lactose and mannose	[76]
5-Iodo 2^′-deoxyuridine 5^′-monophosphate	Lactose	Bioavailability of 5-iodo 2^′-deoxyuridine 5^′-monophosphate to the parenchymal liver cell is dramatically enhanced as a result of the conjugation of the antiviral drugs to lactosylated poly-L-lysine	[31, 77]
Dextran	Permanent magnets and calcein as a fluorescent marker	Dextran magnetite (DM)-incorporated thermosensitive liposomes would be useful in future cancer treatment by magnetic targeting combined with drug release in response to hyperthermia	[78]
Tyr^3-octreotide (TOC), a somatostatin analogue	𝑁-palmitoyl cysteinyl moiety	Tyr^3-octreotide (TOC), a somatostatin analogue shows enhanced therapeutic efficacy due to the liver-targeting effect when coupled with 𝑁-palmitoyl cysteinyl moiety.	[79]
Methotrexate conjugated with bovine serum albumin (BSA)	Galactose	Galactosylation of the carrier protein BSA significantly enhanced the hepatocytes uptake and liver targetability of MTX	[80]
Prednisone acetate conjugated with polycaprolactone-g-dextran polymer	Galactose and fluorescein isothiocyanate	In vivo study indicated potential of prednisone acetate loaded galactosylated micelles in liver targeting	[81]
Lactobionic conjugated with chitosan	Azide (CHI-Az) or alkyne (CHI-Alk) groups	Lactobionic acid was conjugated with (CHI-Az/CHI-Alk)-coated particles and the particles exhibited hepatoma cell (HepG2) targeting behavior	[82]
Doxorubicin	Soybean-derived sterylglucoside (SG)	SG liposomes are potentially useful drug carriers to the liver, because the glucose residue may work as a kind of ligand for asialoglycoprotein receptor (ASGP-R) on hepatocytes	[63]
Primaquine phosphate conjugated with polypropyleneimine (PPI) dendrimers	Coated peripherally with galactose	The galactose coating of PPI dendrimers can make the PPI systems more effective and suitable for targeted delivery of primaquine phosphate to liver	[83]
Paclitaxel conjugated with PLGA	Galactose	Paclitaxel loaded galactosylated PGA-PLA nanoparticles were mainly accumulated at the tumor site and the liver	[84]
Rhein	Vinegar-baked Radix Bupleuri	Co-administration of rhein with VBRB efficient for liver targeting	[85]
Streptavidin	Trinitrophenyl (TNP) groups	The modified proteins could target high doses of chemotherapeutic drugs (CDDP and 5-fluorouridine) to the liver through biotinyl dextran-derived carriers	[86]
5-Fluoro 29-deoxyuridine conjugated with lactosaminated poly-L-lysine	Lactose	Poly-L-lysine-5-fluoro-2^′-deoxyuridine enters into HepG2 cells through the asialoglycoprotein receptor and, after intracellular penetration, releases the drug in a pharmacologically active form	[87]