Carbohydrate-Based Materials for Targeted Delivery of Drugs and Genes to the Liver

Abstract

The insult to liver by toxic materials leads to cirrhosis, hepatitis and cancer. Upon administration, drugs accumulate in liver, which is systemically cleared by reticuloendothelial system. However, specific targeting of drugs to liver is a serious challenge. Specific delivery of molecules to hepatocytes is accomplished by targeting cell surface lectins, asialoglycoprotein receptors. Asialofetuin, N-acetyl glucosamine and galactose are high-affinity ligands of asialoglycoprotein receptors. The bioconjugation of drugs, fluorescent molecules and gene delivery vectors with lectin-targeting agents, and their delivery in liver hepatocytes, is discussed. Mannose and N-acetyl glucosamine conjugates are evaluated for their delivery to hepatic stellate and kupffer cells. The glycosylated gene and drug delivery vectors in clinical trials are outlined.

Cyanobacterium-Derived Extracellular Carbohydrate Polymer for the Controlled Delivery of Functional Proteins

“…Sulfated microbial polymers have been studied as site‐specific drug carriers, due to their intrinsic biocompatibility and potential low cost . Other microbial polymers were shown to provide improved site specificity and meet the desired therapeutic needs for colonic diseases or liver‐specific diseases …”

“…[11,12] Other microbial polymers were shown to provide improved site specificity and meet the desired therapeutic needs for colonic diseases [13] or liver-specific diseases. [14] Among microbial EPS, the polymers derived from cyanobacteria have particular features that stand out such as high content in sulfate groups and the presence of one or two uronic acids that contribute to their strong anionic character. [15] Cyanothece sp.…”

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy

“…HA was used to target CD44 receptors overexpressed on the cellular surface of a variety of tumor carcinomas [85,86]. Additionally, GA-conjugated polymer drug delivery systems have recently been shown to actively target the liver to halt the progression of hepatic tumors [87–89]. To evaluate their HA-GA/HA-His dual-targeting strategy, Wu et al tested the toxicity of their DOX-loaded formulation to HepG2 liver cancer cells in vitro through the MTT colorimetric cell proliferation assay.…”

Promising Use of Cyclodextrin-Based Non-Viral Vectors for Gene and Oligonucleotide Drugs

“…Gene-or drugtargeting systems designed to target the liver are usually directed to hepatocytes, which overexpress ASGPRs on their cell surface. These ASGPRs mediate the removal of potentially hazardous glycoconjugates from the blood; therefore, ASGPRs are usually targeted using galactose residues coupled with a core molecule to enhance binding [49,50]. Many approaches, including but not limited to (1) intravenous injection of pDNA within liposomes [51,52] or via ASGPR targeting [53] and (2) intra-portal injection of recombinant adenovirus [54] and retroviral vectors [55] have been adopted to deliver foreign genes in vivo to hepatocytes.…”