title: Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives.
abstract: Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non-immunogenic and non-inflammatory linear polysaccharide, which has been used for various medical applications such as arthritis treatment, ocular surgery, tissue augmentation, and so on. In this review, the effect of chemical modification of HA on its distribution throughout the body was reported for target specific and long-acting delivery applications of protein, peptide, and nucleotide therapeutics. According to the real-time bio-imaging of HA derivatives using quantum dots (QDot), HA-QDot conjugates with 35mol% HA modification maintaining enough binding sites for HA receptors were mainly accumulated in the liver, while those with 68mol% HA modification losing much of HA characteristics were evenly distributed to the tissues in the body. The results are well matched with the fact that HA receptors are abundantly present in the liver with a high specificity to HA molecules. Accordingly, slightly modified HA derivatives were used for target specific intracellular delivery of nucleotide therapeutics and highly modified HA derivatives were used for long-acting conjugation of peptide and protein therapeutics. HA has been also used as a novel depot system in the forms of physically and chemically crosslinked hydrogels for various protein drug delivery. This review will give you a peer overview on novel HA derivatives and the latest advances in HA-based drug delivery systems of various biopharmaceuticals for further clinical development.
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang 790-784, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Oh
authors.forename: Kitae
authors.initials: K
authors.lastname: Park
authors.forename: Ki Su
authors.initials: KS
authors.lastname: Kim
authors.forename: Jiseok
authors.initials: J
authors.lastname: Kim
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Yang
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kong
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Allan S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry*; D001702:Biopharmaceutics / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D015394:Molecular Structure; D009711:Nucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D045663:Quantum Dots; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D009711:Nucleotides; D010455:Peptides; D004364:Pharmaceutical Preparations; D011506:Proteins; D006820:Hyaluronic Acid