Jeoung Soo Lee, Ph.D.
Research Assistant Professor
B.S. Pharmacy, 1986, Pusan National University
M.S. Pharmaceutics, 1994, Pusan National University
Ph.D. Pharmaceutics, 1999, Pusan National University
Postdoctorate, Pharmeceutical Science, 2003, Univ. of Utah
Postdoctorate, Bioengineering, 2006, Clemson University
M.S. Pharmaceutics, 1994, Pusan National University
Ph.D. Pharmaceutics, 1999, Pusan National University
Postdoctorate, Pharmeceutical Science, 2003, Univ. of Utah
Postdoctorate, Bioengineering, 2006, Clemson University
Research Interests
Polymeric micelle nanoparticle system for drug/gene delivery
Colon-specific drug delivery system
Development of drug- loaded cyanoacrylate tissue adhesives
Colon-specific drug delivery system
Development of drug- loaded cyanoacrylate tissue adhesives
Email:
Office: 313-1 Rhodes Research Center
Phone: 864.656.0278
Office: 313-1 Rhodes Research Center
Phone: 864.656.0278
Laboratory
Honors, Awards, and Professional Activities
Graduate Fellowship Award, Korea Research Fountain (KRF) 1998 Society Memberships:
Society For Biomaterials, SFBAmerican Society of Gene Therapy, ASGTAmerican Association of Pharmaceutical Scientists, AAPSControlled Release Society, CRSCurrent Research
Polymeric Micelle Nanoparticle Delivery System
Amphiphilic di-block copolymers spontaneously self-assemble in aqueous solutions to form nanometer (10-200 nm) scale polymeric micelles. These nanoparticles are characterized by their unique core-shell structures, where hydrophobic segments are segregated from the aqueous exterior to form an inner core surrounded by hydrophilic segments. Novel biodegradable amphiphilic di-block copolymers based on poly (lactide-co-glycolide) (PLGA) and linear polyethylenimine (l-PEI) are designed as a carrier for nucleic acid therapeutics. PLGA is used as hydrophobic core forming blocks and linear PEI is used as hydrophilic shell forming block to condense genes (pDNA, antisense ODN, or siRNA) via electrostatic interaction and to enhance the release of genes internalized into endosome/lysosome by buffering this compartment. The terminal amine group of PEI is used to conjugate targeting moiety to selectively target micelle/gene complexes to unique cell surface molecules expressed by specific cell types.
Application 1. Delivery of gene-based therapeutics for spinal cord regeneration
An emerging strategy for promoting CNS axonal regeneration is the delivery of therapeutic agents that counteract or block the function of myelin-associated inhibitory proteins such as Nogo A, myelin associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp). The objective of this research is the development of mixed polymeric micelles for simultaneous delivery of two therapeutic agents (antisense oligodeoxynucleotide and antibody) directed at reducing the activity of the Nogo-66 receptor (NgR), which is a common receptor of myelin-associated proteins. This dual strategy will be based on interference with the function of existing NgR at the protein level and inhibition of further production of new NgR synthesis at the genetic level.
Application 2. Polymeric micelle as a drug and gene combination therapy tool for cancer treatment
Polymeric micelles have been used for anticancer drug delivery carrier due to their long- circulating characteristics in the blood and delivery of the anticancer drugs to the tumor site by EPR (enhanced permeation and retention) effect. The novel mixed di-block polymeric micelle, PLGA-b-PEI and PLGA-b-PEI-Tg (Tg:targeting moiety) can be used for the delivery of hydrophobic anticancer drug and tumor suppressor gene to the tumor site for the combination cancer therapy. This system will provide hydrophobic core as a drug reservoir and hydrophilic shell as a gene carrier which has specific tumor targeting moiety at the surface of micelle.
Application 1. Delivery of gene-based therapeutics for spinal cord regeneration
An emerging strategy for promoting CNS axonal regeneration is the delivery of therapeutic agents that counteract or block the function of myelin-associated inhibitory proteins such as Nogo A, myelin associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp). The objective of this research is the development of mixed polymeric micelles for simultaneous delivery of two therapeutic agents (antisense oligodeoxynucleotide and antibody) directed at reducing the activity of the Nogo-66 receptor (NgR), which is a common receptor of myelin-associated proteins. This dual strategy will be based on interference with the function of existing NgR at the protein level and inhibition of further production of new NgR synthesis at the genetic level.
Application 2. Polymeric micelle as a drug and gene combination therapy tool for cancer treatment
Polymeric micelles have been used for anticancer drug delivery carrier due to their long- circulating characteristics in the blood and delivery of the anticancer drugs to the tumor site by EPR (enhanced permeation and retention) effect. The novel mixed di-block polymeric micelle, PLGA-b-PEI and PLGA-b-PEI-Tg (Tg:targeting moiety) can be used for the delivery of hydrophobic anticancer drug and tumor suppressor gene to the tumor site for the combination cancer therapy. This system will provide hydrophobic core as a drug reservoir and hydrophilic shell as a gene carrier which has specific tumor targeting moiety at the surface of micelle.
Colon-specific Bi-fuctional Polymeric Prodrug for Treatment of Amebiasis
Site-specific drug delivery aims to selectively deliver therapeutic agents to target tissue/organ in order to increase therapeutic efficiency and reduce the systemic side effect of drugs. Colon-specific prodrugs are one way to deliver drugs specifically to the colon for the efficient treatment of diseases developed in the colon such as colorectal cancer, Chron’s disease, ulcerative colitis, and intestinal infection by bacteria. To develop colon-specific prodrugs, polymeric or water-soluble carriers are employed to prevent absorption of prodrug in the upper GI tract. After delivery to the colon, the prodrug is activated by enzymes produced from the microbes which reside in the lower intestine. This project is focused on development of a novel bi-functional polymeric amebicidal therapeutic, Galactose-Dextran-Metronidazole (Gal-Dextran-MM) conjugates, for treatment of amebiasis. This amebicidal therapeutic is designed to block disease progression and eradicate the underlying infection through two mechanisms, 1) delivery of the amebicidal agent, metronidazole, to kill the infected Amoeba, 2) delivery of galactose which can inhibit host cell-parasite adhesion. The main hypothesis is that the release of metronidazole and galactose from Gal-Dextran-MM conjugates does not take place in upper GI tract because the steric hindrance of the polymer prevents the enzymatic hydrolysis from the dextran backbone and release of drug takes place from only oligomerized Gal-Dextran-MM, which is formed by depolymerization of the dextran matrix by dextranase in the colon.
Development of Bioabsorbable Alkylcyanoacrylate Tissue Adhesives for Internal Application
Cyanoacrylate tissue adhesives are liquid monomers that rapidly polymerize on contact with tissue creating thin flexible films capable of closing wounds and maintaining a natural healing environment. Cyanoacrylates with short alkyl side chains such as methyl-, ethyl- isopropyl,- were investigated as tissue adhesives but were replaced by longer-chain cyanoacrylate such as butyl-, and octyl cyanoacrylate. While short chain cyanoacrylates exhibited rapid degradation, this was associated with significant tissue toxicity and inflammation. Octyl cyanoacrylate received FDA approval in 1998 for topical wound closure after lacerations or incisions. However, their use is limited to external wounds because of their extremely slow biodegradtion, although they have advantages as internal adhesives, such as very rapid cure time and excellent bond strength relative to other adhesives (fibrin, collagen, and albumin-based glue). The objective of this research project is the development of cyanoacrylate adhesives with increased degradability for internal applications. Two approaches are being investigated: 1) the creation of novel formulations of cyanoacrylates with other polymers that will accelerate degradability and 2) the synthesis of new cyanoacrylate-type monomers with bond chemistry exhibiting increased susceptibility to hydrolytic degradation.
Development of Drug-loaded Alkylcyanoacrylate Tissue Adhesives
The applications and capabilities of cyanoacrylate tissue adhesives may be greatly improved by the incorporation of various drugs into the adhesive and their subsequent controlled release. Many useful drugs are with physically immiscible with hydrophic cyanoacrylate monomers or chemically incompatible due to the presence of amine groups that initiate cyanoacrylate polymerization. The objective of this research project is to develop novel strategies for incorporating drugs in cyanoacrylate monomers. The advantages of drug-loaded tissue adhesives are first, local drug delivery avoids side effects of systemic drug delivery. Second, tissue adhesive plays a role as a reservoir for drug and drug can release controlled manner from the adhesive depending on the degradation rate of CA polymer. Therefore, frequent treatment is not necessary like topical antibiotic cream or solution. Third, high concentration of drug in the wound area can be achieved. Two potential applications are currently envisioned: 1) loading of cyanoacrylate with antibiotic drugs to increase their effectiveness as barriers to infection and 2) loading of anticancer drugs for wound closure following removal of dermal malignant growths.
Recent Publications
Young Wook Yang, Jeoung Soo Lee, Inho Kim, and Young Mi Kim. Synthesis and properties of N-nicotinoyl-2-(5-fluorouracil-1-yl)-D,L-glycine ester as a prodrug of 5-fluorouracil for rectal administration. European Journal of Pharmacutics and Biopharmaceutics (2006), Epub ahead of print
Jeoung Soo Lee, Dina M. Basalyga, Agneta Simionescu, Jason C. Isenburg, Dan T. Simionescu, and Narendra R. Vyavahare. Elastin calcification in the rat subdermal model is accompanied by upregulation of degradative and osteogenic cellular responses. Am J. Pathol, 168 (2), 490-498 (2006)
Dan T. Simionescu, Quijin Lu, Ying Song , Jeoung Soo Lee, TN Rosenbalm, C Kelly, and Naren Vyavahare, Biocompatibility and remodeling potential of pure arterial elastin and collagen scaffolds. Biomaterials, 27(5), 702-713 (2006)
Jeoung Soo Lee, Minhyung Lee, and Sung Wan Kim, A New Potent hFIX Plasmid for Hemophilia B Gene Therapy, Pharm. Res., 21(7), 1229-1232 (2004)
Yun Jin Jung, Minju Doh, Haesik Kong, Jeoung Soo Lee and Young Mi Kim Prednisolone 21-sulfate sodium: a colon-specific pro-drug of prednisolone, J Pharm Pharmacology, 55 (8), 1075-1082 (2003)
Jeoung Soo Lee, Yun Jin Jung, Hak Hyun Kim, and Young Mi Kim, Development of a Colon-specific Prodrug of 5-Fluorouracil: Synthesis and Properties of N-Nicotinyl-2-(5-Fluorouracil-1-yl)-D,L-Glycine. J. Pharm. Sci., 90 (11), 1787-1794 (2001)
