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67. Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug

Author

Lim,Chaemin, Shin,Yuseon, Kang,Kioh, Husni,Patihul, Lee,Dayoon, Lee,Sehwa, Choi,Han-Gon, Lee,Eun Seong, Youn,Yu Seok, Oh,Kyung Taek, Lim,Chaemin, Shin,Yuseon, Kang,Kioh, Husni,Patihul, Lee,Dayoon, Lee,Sehwa, Choi,Han-Gon, Lee,Eun Seong, Youn,Yu Seok, and Oh,Kyung Taek

Abstract

Chaemin Lim,1,* Yuseon Shin,2,* Kioh Kang,2 Patihul Husni,2 Dayoon Lee,2 Sehwa Lee,2 Han-Gon Choi,3 Eun Seong Lee,4 Yu Seok Youn,5 Kyung Taek Oh1,2 1College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea; 2Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, Seoul, 06974, Republic of Korea; 3College of Pharmacy, Hanyang University, Ansan, 15588, South Korea; 4Department of Biotechnology, The Catholic University of Korea, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; 5School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea*These authors contributed equally to this workCorrespondence: Kyung Taek Oh, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, 06974, Republic of Korea, Tel +82-2-824-5617, Email kyungoh@cau.ac.krIntroduction: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand.Methods: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo.Results: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by > 40% in the Dox

Published
2023

68. Molecular dynamics interpretation of hydrogen bonds for colorless, water-resistant, tough, and self-healable elastomers.

Author

Kim, Seon-Mi, Lee, Minkyung, Park, Sanggil, Park, Seul-A., Jeon, Hyeonyeol, Koo, Jun Mo, Park, Sung Bae, Kim, Hyo Jeong, Eom, Youngho, Lee, Eun Seong, Kim, Hyungjun, Oh, Dongyeop X., and Park, Jeyoung

Abstract

Transparent, self-healing elastomers play a vital role as protective coatings, particularly in display applications. However, mechanical toughness and efficient self-restoration are often mutually exclusive. A performance equilibrium can be achieved through the molecular design of reversible bonds. However, aromatic disulfide-based dynamic covalent bonds produce an unattractive coloration owing to electron chromophores. In addition, H-bond moieties induce unintended adhesion to the substrates and are limited by hydration-induced weakening. In this study, the molecular design of aliphatic disulfides is presented for colorless, non-tacky, and water-resistant elastomers that rapidly self-heal at ambient temperatures. By employing molecular dynamics simulations, we demonstrate that an excess of H-bond acceptors promotes shorter bond exchange durations while maintaining a higher quantity of cohesive H-bonds, surpassing the performance of equivalent donor/acceptor systems at identical donor concentrations. In addition, dynamic H-bond exchange enables effective healing, whereas the increased H-bond cross-linking density ensures both waterproofness and an impressive tensile strength of 45 MPa. Furthermore, the absence of aromatic groups grants the elastomers a remarkable transmittance of 99%. The optimized properties achieved in this study using the proposed strategic molecular designs will further the commercialization of self-healing thermoplastic polyurethanes as intelligent protective coatings. [ABSTRACT FROM AUTHOR]

Published
2023
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69. pH‐dependent swellable hyaluronate nanogels targeting acidic tumors.

Author

Song, Jeonghun, Lee, Eunsol, and Lee, Eun Seong

Subjects
NANOGELS, ADIPIC acid, HYALURONIC acid, TUMORS, PROPYLAMINE
Abstract

In this study, we have developed pH‐dependent nanogels based on hyaluronic acid (HA) to specifically target acidic tumors. Our initial approach involved modifying HA through the grafting of 3‐(diethylamino)propylamine (DEAP), a molecule known for its responsiveness to changes in pH. This modified HA was termed as HDEA. Subsequently, we performed chemical crosslinking of HDEA using adipic acid dihydrazide (ADH), a crosslinking molecule, resulting in the formation of nanogels referred to as cHDEA. Importantly, the non‐ionized DEAP molecules (with a pKb value of ~pH 7.0) at pH 7.4 support the formation of deswellable cHDEA. This property enables the encapsulation of a photodynamic model drug, chlorin e6 (Ce6), into cHDEA. However, when the DEAP molecules become protonated at pH 6.8, they induce a change in the nanogel structure, causing it to swell due to electrostatic repulsion. As a result, Ce6 is rapidly released from the nanogels. By modulating the pH, we can continuously control the nanogel structure, alternating between swelling and deswelling states. We anticipate that this system offers the advantage of facilitating drug release specifically under acidic tumor conditions while inhibiting drug release under normal pH conditions (i.e., pH 7.4). This approach will serve as an effective strategy for mitigating side effects by efficiently controlling drug release in specific disease areas. [ABSTRACT FROM AUTHOR]

Published
2023
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75. 11C-Pittsburgh B PET Imaging in Cardiac Amyloidosis

Author

Lee, Seung-Pyo, Lee, Eun Seong, Choi, Hongyoon, Im, Hyung-Jun, Koh, Youngil, Lee, Min-Ho, Kwon, Ji-Hyun, Paeng, Jin Chul, Kim, Hyung-Kwan, Cheon, Gi Jeong, Kim, Yong-Jin, Kim, Inho, Yoon, Sung-Soo, Seo, Jeong-Wook, and Sohn, Dae-Won

Published
2015
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