title: Erythropoietin gene delivery using an arginine-grafted bioreducible polymer system.
abstract: Erythropoietin (EPO) plays a key regulatory role in the formation of new red blood cells (RBCs). Erythropoietin may also have a role as a therapeutic agent to counteract ischemic injury in neural, cardiac and endothelial cells. One of the limitations preventing the therapeutic application of EPO is its short half-life. The goal of this study was to develop a gene delivery system for the prolonged and controlled release of EPO. The arginine grafted bioreducible polymer (ABP) and its PEGylated version, ABP-PEG10, were utilized to study the expression efficiency and therapeutic effectiveness of this erythropoietin gene delivery system in vitro. Poly(ethylene glycol) (PEG) modification of the ABP was employed to inhibit the particle aggregation resulting from the interactions between cationic polyplexes and the negatively charged proteins typically present in serum. Both the ABP and the ABP-PEG10 carriers demonstrated efficient transfection and long-term production of EPO in a variety of cell types. The expressed EPO protein stimulated hematopoietic progenitor cells to form significant numbers of cell colonies in vitro. These data confirm that this EPO gene delivery system using a bioreducible polymeric carrier, either ABP or ABP-PEG 10, merits further testing as a potential therapeutic modality for a variety of clinically important disease states.
authors: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, United States.
authors: Hye Yeong
authors: HY
authors: Nam
authors: Youngsook
authors: Y
authors: Lee
authors: Minhyung
authors: M
authors: Lee
authors: Sug Kyun
authors: SK
authors: Shin
authors: Tae-il
authors: TI
authors: Kim
authors: Sung Wan
authors: SW
authors: Kim
authors: David A
authors: DA
authors: Bull
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D004921:Erythropoietin / Q000235:genetics*; D006461:Hemolysis / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods
chemical_list: D004337:Drug Carriers; D011108:Polymers; D004921:Erythropoietin; D004247:DNA; D001120:Arginine