Hye Ri Lee

Poly(PEGA)-b-poly(l-lysine)-b-poly(l-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride

A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine)-block-poly(L-histidine) [p(PEGA)30-b-p(Lys)25-b-p(His)n] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 μg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery.

Efficient, Solvent-Free, Multicomponent Method for Organic-Base-Catalyzed Synthesis of β-Phosphonomalonates

An efficient, one-pot, di-n-butylamine-catalyzed, three-component synthesis of β-phosphonomalonates has been developed. A wide range of substrates, including aromatic and fused aromatic aldehydes, were condensed with enolizable C-H activated compounds and dialkylphosphites to give the desired products in excellent yields. This method provides an eco-friendly alternative approach to rapid construction of a diversity-oriented library of β-phosphonomalonates.

Phospho sulfonic acid: an efficient and recyclable solid acid catalyst for the solvent-free synthesis of α-hydroxyphosphonates and their anticancer properties

As a means of developing biologically active compounds, a series of α-hydroxyphosphonates, ArC(OH)PO(OR)2 (Ar = 5-G-2-OHPh; R = Me, Et, iPr, Bu; G = H, Br, Cl, NO2), have been synthesized by reacting diversely substituted salicylaldehydes with dialkyl phosphites by employing the Pudovik reaction in the presence of phospho sulfonic acid under neat conditions. The cytotoxicity of the compounds was tested in two human cancer cell lines by using MTT assay. Compounds bearing R = Et; G = Cl, R = Bu; G = Cl, and R = Et; G = NO2 showed good anticancer activity.

Phospholipid End-Capped Acid-Degradable Polyurethane Micelles for Intracellular Delivery of Cancer Therapeutics

Nanoscale drug carriers fabricated by phospholipid end-capped polyurethane bearing acetal backbones that degrade in acidic conditions are fabricated. These micelles effectively allow drugs to enter the blood circulation, and then disintegrate in acidic endosomes and lysosomes for intelligent delivery of payloads.

Hyperbranched polyglycidol/phosphatidylcholine and phosphatidylethanolamine hybrid liposomes for the pH-sensitive delivery of doxorubicin.

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Self-aggregates of hyperbranched epoxidized 2-hydroxyethyl methacrylate conjugates of methotrexate: Synthesis and in vitro drug delivery.

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Phosphatidylethanolamine polyglycidol bioconjugates for controlled drug delivery.

In recent years, there has been tremendous growth in the development of lipid based delivery systems due to the increasing demands for biocompatible drug carriers [1]. Especially, lipid based carriers of biological origin offer many advantages for an ideal delivery vehicle such as biocompatibility and biodegradability. However, potential disadvantages such as poor drug loading capacity, their particle growing, unpredictable gelation tendency, drug expulsion after polymeric transition during storage and relatively high water content of the dispersions have been observed. In order to overcome these problems, we have focused on the synthesis of a lipid conjugated amphiphilic bioconjugate chimeric material for the delivery of hydrophilic/hydrophobic anticancer drugs. Using amine groups on the head of phosphatidylethanolamine (PE), which has been extracted and purified from commercial soybean lecithin, as an initiator, ring-opening multi-branching polymerizations of glycidol were performed [2], resulting in lipid-hyperbranched polyglycidol (HBP) bioconjugates. Molecular weight (MW) of HBP was controlled from 150 to 1000. The PE–HBP hybrids were fully characterized by various spectroscopic techniques and then PE–HBP vesicles were fabricated by the self-assembly process in ethanol–water solvent combinations (Fig. 1). Highly uniform vesicles with a diameter ranging from70 nm to 120 nmwere formed and tunable according to theMWof HBP. The amphiphilic nature of the PE–HBP hybrids increased hydrophilic/hydrophobic drug loading capacities with no gelation tendency and drug expulsion. According to drug loading and drug delivery tests using doxorubicin (DOX), these novel lipopolymer hybridmaterials have a potential to be used as valuablematerials for drug delivery applications without any cytotoxicity.