title: Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane.
abstract: Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
authors.forename: Eung-Sam
authors.initials: ES
authors.lastname: Kim
authors.forename: Do Soo
authors.initials: DS
authors.lastname: Jang
authors.forename: Seung Yun
authors.initials: SY
authors.lastname: Yang
authors.forename: Mi Nam
authors.initials: MN
authors.lastname: Lee
authors.forename: Kyeong Sik
authors.initials: KS
authors.lastname: Jin
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Cha
authors.forename: Jin Kon
authors.initials: JK
authors.lastname: Kim
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Kwan Yong
authors.initials: KY
authors.lastname: Choi
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000378:metabolism; D008567:Membranes, Artificial; D010766:Phosphorylation / Q000187:drug effects; D016062:Porosity; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D007072:Immunoglobulin D; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D008567:Membranes, Artificial; D011993:Recombinant Fusion Proteins; D019382:Human Growth Hormone; C507924:JAK2 protein, human; D053614:Janus Kinase 2