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Kim Kwangmeyung,Kim Jong-Ho,Kim Sungwon,Chung Hesson,Choi Kuiwon,Kwon Ick Chan,Park Jae Hyung,Kim Yoo-Shin,Park Rang-Won,Kim In-San,Jeong Seo Young The Polymer Society of Korea 2005 Macromolecular Research Vol.13 No.3
This review explores recent works involving the use of the self-assembled nanoparticles of bile acid-modified glycol chitosans (BGCs) as a new drug carrier for cancer therapy. BGC nanoparticles were produced by chemically grafting different bile acids through the use of l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). The precise control of the size, structure, and hydrophobicity of the various BGC nanoparticles could be achieved by grafting different amounts of bile acids. The BGC nanoparticles so produced formed nanoparticles ranging in size from 210 to 850 nm in phosphate-buffered saline (PBS, pH=7.4), which exhibited substantially lower critical aggregation concentrations (0.038-0.260 mg/mL) than those of other low-molecular-weight surfactants, indicating that they possess high thermodynamic stability. The SOC nanoparticles could encapsulate small molecular peptides and hydrophobic anticancer drugs with a high loading efficiency and release them in a sustained manner. This review also highlights the biodistribution of the BGC nanoparticles, in order to demonstrate their accumulation in the tumor tissue, by utilizing the enhanced permeability and retention (EPR) effect. The different approaches used to optimize the delivery of drugs to treat cancer are also described in the last section.
Tumor-Targeting Multifunctional Nanoparticles for siRNA Delivery: Recent Advances in Cancer Therapy
Ku, Sook Hee,Kim, Kwangmeyung,Choi, Kuiwon,Kim, Sun Hwa,Kwon, Ick Chan Wiley (John WileySons) 2014 Advanced Healthcare Materials Vol.3 No.8
<P>RNA interference (RNAi) is a naturally occurring regulatory process that controls posttranscriptional gene expression. Small interfering RNA (siRNA), a common form of RNAi-based therapeutics, offers new opportunities for cancer therapy via silencing specific genes, which are associated to cancer progress. However, clinical applications of RNAi-based therapy are still limited due to the easy degradation of siRNA during body circulation and the difficulty in the delivery of siRNA to desired tissues and cells. Thus, there have been many efforts to develop efficient siRNA delivery systems, which protect siRNA from serum nucleases and deliver siRNA to the intracellular region of target cells. Here, the recent advances in siRNA nanocarriers, which possess tumor-targeting ability are reviewed; various nanoparticle systems and their antitumor effects are summarized. The development of multifunctional nanocarriers for theranostics or combinatorial therapy is also discussed.</P>
Nano-enabled delivery systems across the blood-brain barrier
Hwang, Seung Rim,Kim, Kwangmeyung 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.1
The development of drugs to treat disorders of the central nervous system (CNS) faces difficulties in achieving penetration of a drug through the blood-brain barrier (BBB) and allowing the drug to reach its intended target in the brain. There have been strategies to improve drug delivery to the brain through endogenous transport pathways such as passive diffusion, endocytosis, and active transport. Among various strategies, nano-enabled delivery systems offer a promising solution to improve the uptake and targeted delivery of drugs into the brain. Various nanocarriers including liposomes, bolaamphiphiles and nanoparticles can be used as a means to encapsulate drugs, either alone or in combination with targeting ligands. Moreover, most of materials used in nanocarrier fabrication are both biodegradable and biocompatible, thereby increasing the clinical utility of them. Here, we review the possibility to employ nano-enabled materials for delivery of drug across the BBB and the recent advances in nanotechnologies for therapy of the CNS diseases.
Choi, Kyung-mi,Kim, Kwangmeyung,Kwon, Ick Chan,Kim, In-San,Ahn, Hyung Jun American Chemical Society 2013 Molecular pharmaceutics Vol.10 No.1
<P>Recently, we reported that a chimeric capsid protein assembled into a macromolecular container-like structure with capsid shell and the resulting siRNA/capsid nanocarrier complexes efficiently suppressed RFP gene expression in the cell culture system. To extend RNAi to the <I>in vivo</I> applications, we here demonstrated that the siRNA/capsid nanocarrier complexes could have tumor-specific targeting ability <I>in vivo</I> as well as the increased stability of siRNA during body circulation. When systemically administered, our siRNA/capsid nanocarrier complexes delivered siRNA to tumor tissues and efficiently suppressed RFP gene expression in tumor-bearing mice. The enhanced longevity of siRNA <I>in vivo</I> could be explained by shielding effect derived from the capsid shell, where the encapsulated siRNAs are protected from nucleases in plasma. The multivalent RGD peptides on shell surface, as a result of self-assembling of capsid protein subunits, showed efficient delivery of siRNA to the tumor tissues <I>in vivo</I>, due to the RGD-mediated binding to integrin receptors overexpressed on tumor cells. Moreover, the prolonged <I>in vivo</I> circulation time of our siRNA/capsid nanocarrier complexes increased the potential to serve as siRNA carriers for optimal <I>in vivo</I> RNAi. These results provide an alternative approach to systemically deliver siRNA to the tumor sites as well as to enhance the stability of siRNA <I>in vivo</I>. Therefore, our results revealed the promising potential of our capsid nanocarrier system as a therapeutic siRNA carrier for cancer treatment.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2013/mpohbp.2013.10.issue-1/mp300211a/production/images/medium/mp-2012-00211a_0003.gif'></P>
Krishna, Ohm Divyam,Jeon, Ok Cheol,Kim, Kwangmeyung,Byun, Youngro,Moon, Hyun Tae Informa UK (TaylorFrancis) 2010 Journal of biomaterials science, Polymer edition Vol.21 No.6
<P>We have prepared a covalently-grafted phsopholipid/PEG mixed monolayer onto drug-loaded polymercoated stainless-steel stents by in situ polymerization. To introduce a biocompatile surface on the stent surface, AcPC (1-palmitoyl-2-[12-(acryloyloxy)dodecanoyl]-sn-glycero-3-phosphocholine) and AcPEG (12-(acryloyloxy)dodecanoyl-poly(ethylene glycol)) were synthesized by modifying phospholipid and PEG with 12-(acryloyloxy)-1-dodecanoic acid and 12-(acryloyloxy)-1-dodecanol, respectively. Also, an acrylated co-polymer was synthesized by the acrylation of poly(octadecyl acrylate-co-hydroxybutyl acrylate, poly(OA-co-HA)) with acryloyl chloride, and poly(OA-co-HA) loaded with a hydrophobic drug, echinomycin, was coated on the stent surface using a spray coating system. In situ polymerization was carried out at the interface between a pre-assembled AcPC/AcPEG mixture and the enchinomycin-loaded acrylated co-polymer-coated stainless steel (Pol-SS). The physicochemical properties of a covalently-grafted phsopholipid/PEG mixed monolayer onto the drug-loaded polymer-coated stainless-steel stents were evaluated using water contact angle, field-emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS). The data confirmed a successful phsopholipid/PEG monolayer grafting on the stents surface. The drug-release profile showed a sustained and controllable release pattern by the top-coated stents, achieved by adjusting the amount of loaded drug.</P>