The Experts below are selected from a list of 606 Experts worldwide ranked by ideXlab platform
Dae-duk Kim - One of the best experts on this subject based on the ideXlab platform.
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Mussel-Inspired Hyaluronic Acid Derivative Nanostructures for Improved Tumor Targeting and Penetration
ACS applied materials & interfaces, 2017Co-Authors: Song Yi Lee, Ju-hwan Park, Jae-seong Shim, Dae-duk Kim, Hyun-jong ChoAbstract:An amphiphilic Hyaluronic Acid-ceramide-dopamine (HACE-d) conjugate was prepared, and HACE-d-based nanoparticles (NPs) including phloretin (as an inhibitor of glucose transporter (GLUT1)) were fabricated. Mussel-inspired property of d was introduced to HACE NPs, and it may improve tumor targetability and penetration in addition to passive (based on enhanced permeability and retention effect) and active (interaction between HA and CD44 receptor) tumor targeting effects. HACE-d/phloretin NPs with 279 nm mean diameter, ∼0.2 polydispersity index, and −18 mV zeta potential were successfully fabricated, and a sustained drug release pattern was observed. HACE-d/phloretin NPs exhibited enhanced cellular accumulation efficiency and antiproliferation property, compared with HACE/phloretin NPs, in MDA-MB-231 cells (GLUT1 and CD44 receptor-expressed human breast adenocarcinoma cells). In a MDA-MB-231 spheroid model, HACE-d NPs group showed better tumor penetration efficiency and spheroid growth inhibitory effect rath...
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Boronic Acid-tethered amphiphilic Hyaluronic Acid Derivative-based nanoassemblies for tumor targeting and penetration.
Acta biomaterialia, 2017Co-Authors: Jae Young Jeong, Jae Young Lee, Jae-seong Shim, Song Yi Lee, Eun-hye Hong, Jae-hyoung Song, Sunghwa Choe, Dae-duk KimAbstract:(3-Aminomethylphenyl)boronic Acid (AMPB)-installed Hyaluronic Acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic Acid group of Hyaluronic Acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic Acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic Acid-sialic Acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic Acid-sialic Acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic Acid (AMPB)-tethered Hyaluronic Acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic Acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous milieu) may react with the sialic Acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic Acid-sialic Acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery
Colloids and surfaces. B Biointerfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery B Biointerfaces
Colloids and Surfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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nanocomplexes based on amphiphilic Hyaluronic Acid Derivative and polyethylene glycol lipid for ginsenoside rg3 delivery
Journal of Pharmaceutical Sciences, 2014Co-Authors: Jae Young Lee, Hyun-jong Cho, Jae-seong Shim, In-soo Yoon, Heejung Yang, Sangbum Kim, Sang Hyun Sung, Dae-duk KimAbstract:Hybrid nanocomplex formulations, based on amphiphilic Hyaluronic Acid–ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents.
Hyun-jong Cho - One of the best experts on this subject based on the ideXlab platform.
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Mitochondria Targeting and Destabilizing Hyaluronic Acid Derivative-Based Nanoparticles for the Delivery of Lapatinib to Triple-Negative Breast Cancer
Biomacromolecules, 2018Co-Authors: Song Yi Lee, Hyun-jong ChoAbstract:CD44 receptor and mitochondria targeting Hyaluronic Acid-d-α-tocopherol succinate-(4-carboxybutyl)triphenyl phosphonium bromide (HA-TS-TPP)-based nanoparticles (NPs) were designed for the delivery of lapatinib (LPT) to triple-negative breast cancer (TNBC). While LPT is one of the dual tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR) and human EGFR2 (HER2), TNBC cells often exhibit EGFR positive and HER2 negative patterns. Along with the HER2-independent anticancer activities of LPT in TNBC, apoptosis-inducing properties of TPP and TS (resulting from mitochondrial targeting and destabilization) were introduced to amplify the anticancer activities of HA-TS-TPP/LPT NPs for TNBC. HA-TS-TPP/LPT NPs, with approximately 207 nm mean diameter, unimodal size distribution, spherical shape, negative zeta potential, and sufficient particle stability, were prepared in this study. The improved antiproliferation potential, apoptotic efficacy, and mitochondrial destabilizing activity of HA-TS-TPP/LPT NPs, compared with HA-TS/LPT NPs, were demonstrated in TNBC (i.e., MDA-MB-231) cells. The in vivo tumor targeting capability of HA-TS-TPP/LPT NPs was proven in MDA-MB-231 tumor-bearing mouse models using real-time optical imaging. Of note, HA-TS-TPP/LPT NPs exhibited a better tumor growth suppression profile than the other groups after intravenous injection. It is expected that developed HA-TS-TPP NPs can elevate the therapeutic potential of LPT for TNBC.
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Mussel-Inspired Hyaluronic Acid Derivative Nanostructures for Improved Tumor Targeting and Penetration
ACS applied materials & interfaces, 2017Co-Authors: Song Yi Lee, Ju-hwan Park, Jae-seong Shim, Dae-duk Kim, Hyun-jong ChoAbstract:An amphiphilic Hyaluronic Acid-ceramide-dopamine (HACE-d) conjugate was prepared, and HACE-d-based nanoparticles (NPs) including phloretin (as an inhibitor of glucose transporter (GLUT1)) were fabricated. Mussel-inspired property of d was introduced to HACE NPs, and it may improve tumor targetability and penetration in addition to passive (based on enhanced permeability and retention effect) and active (interaction between HA and CD44 receptor) tumor targeting effects. HACE-d/phloretin NPs with 279 nm mean diameter, ∼0.2 polydispersity index, and −18 mV zeta potential were successfully fabricated, and a sustained drug release pattern was observed. HACE-d/phloretin NPs exhibited enhanced cellular accumulation efficiency and antiproliferation property, compared with HACE/phloretin NPs, in MDA-MB-231 cells (GLUT1 and CD44 receptor-expressed human breast adenocarcinoma cells). In a MDA-MB-231 spheroid model, HACE-d NPs group showed better tumor penetration efficiency and spheroid growth inhibitory effect rath...
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery
Colloids and surfaces. B Biointerfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery B Biointerfaces
Colloids and Surfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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nanocomplexes based on amphiphilic Hyaluronic Acid Derivative and polyethylene glycol lipid for ginsenoside rg3 delivery
Journal of Pharmaceutical Sciences, 2014Co-Authors: Jae Young Lee, Hyun-jong Cho, Jae-seong Shim, In-soo Yoon, Heejung Yang, Sangbum Kim, Sang Hyun Sung, Dae-duk KimAbstract:Hybrid nanocomplex formulations, based on amphiphilic Hyaluronic Acid–ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents.
Gaetano Giammona - One of the best experts on this subject based on the ideXlab platform.
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Multifibrillar bundles of a self-assembling Hyaluronic Acid Derivative obtained through a microfluidic technique for aortic smooth muscle cell orientation and differentiation.
Biomaterials Science, 2018Co-Authors: Fabio Salvatore Palumbo, Calogero Fiorica, Giovanna Pitarresi, Massimiliano Zingales, Emanuela Bologna, Gaetano GiammonaAbstract:A Hyaluronic Acid Derivative that is able to physically crosslink in a saline aqueous environment was employed for the production of fibers with a mean diameter of 50 μm using a microfluidic technique. The microfibers were collected in a tailored rotating collector and assembled to form multifibrillar bundles. The orientation of the microfibers on the collected bundles was evaluated by microCT analysis. The bundles were biofunctionalized by physical addition of fibronectin or chemical tethering of a cyRGDC peptide to achieve control of Aortic Smooth Muscle Cell (AoSMC) attachment, elongation and alignment. The mechanical performances of these bundles were evaluated by elongation tests, related to the kind of biological functionalization and compared to non-functionalized samples. The alignment and differentiation of AoSMCs on single fibers and on the bundles were evaluated by microscopy and histochemical analyses.
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Microfluidic Fabrication of Physically Assembled Nanogels and Micrometric Fibers by Using a Hyaluronic Acid Derivative
Macromolecular Materials and Engineering, 2017Co-Authors: Stefano Agnello, Fabio Salvatore Palumbo, Calogero Fiorica, Giovanna Pitarresi, Flavia Bongiovì, Maria Antonietta Di Bella, Gaetano GiammonaAbstract:The employ of a Hyaluronic Acid (HA) Derivative, bearing octadecyl (C18) and ethylenediamine (EDA) groups, for microfluidic fabrication of nanogels and microfibers is reported in this study. Two HA-EDA-C18 Derivatives (125 and 320 kDa) having ionic strength sensitive properties are synthesized and characterized. The control of the rheological properties of HA-EDA-C18 aqueous dispersions by formation of inclusion complexes with hydroxypropyl-β-cyclodextrins (HPCD) is described. Reversibility of C18/HPCD complexation and physical crosslinking is detected in media with different ionic strength through oscillation frequency tests. HA-EDA-C18 125 kDa is employed for nanogel fabrication. Control over nanogel dimension by flow ratio regulation is demonstrated. HA-EDA-C18 320 kDa with HPCD is employed for fabrication of both microfibers and microchannels. Dimension of fibers is controlled by modulating flow ratios. Suitability for biological functionalization is assayed introducing cell adhesive peptides. Adhesion and encapsulation of human umbilical vein endothelial cells is evaluated.
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a methacrylic Hyaluronic Acid Derivative for potential application in oral treatment of celiac disease
Drug Development and Industrial Pharmacy, 2017Co-Authors: Giovanna Pitarresi, Fabio Salvatore Palumbo, Calogero Fiorica, Daniela Triolo, Gaetano GiammonaAbstract:AbstractObjective: Aim of this work was the synthesis of a methacrylic Hyaluronic Acid (HA) Derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease.Methods: The methacrylic Derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained Derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders.Results: Hydrogels obtained as freeze-dried powders, are able to protect loaded enzyme from degradation due to freeze-drying process and from alteration during storage, overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in sustained ...
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Hyaluronic Acid Derivative with Improved Versatility for Processing and Biological Functionalization.
Macromolecular bioscience, 2016Co-Authors: Fabio Salvatore Palumbo, Calogero Fiorica, Giovanna Pitarresi, Stefano Agnello, Roberto Puleio, Anna Tamburello, Ruggero Loria, Gaetano GiammonaAbstract:A hydrophobic/amino functionalized Derivative of Hyaluronic Acid (HA-EDA-C18 ) has been processed by salt leaching technique as porous scaffold without need of chemical crosslinking. Aim of this work is to demonstrate the improved versatility of HA-EDA-C18 in terms of processing and biological functionalization. In particular, the chemical procedure to tether thiol bearing RGD peptide has been described. Moreover, the possibility to load and to control the release of slightly water soluble effectors has been demonstrated by using dexamethasone. First, the swelling and degradation profiles of the scaffolds have been investigated, then the evaluation of metabolic activity of bovine chondrocytes, the histological analysis, and microscope observations has been performed to evaluate cellular adhesion and proliferation as well as the production of collagen type II.
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Microfluidic production of Hyaluronic Acid Derivative microfibers to control drug release
Materials Letters, 2016Co-Authors: Stefano Agnello, Fabio Salvatore Palumbo, Giovanna Pitarresi, Luca Gasperini, Rui L. Reis, João F. Mano, Gaetano GiammonaAbstract:Microfibers of a Hyaluronic Acid amphiphilic Derivative (HA-EDA-C18), with incorporated dexamethasone (Dex) as a model bioactive molecule, were obtained by microfluidic technique. Exploiting the ionic strength sensible behavior of HA-EDA-C18, microfibers were formed in baths containing phosphate buffer saline with different salt concentration. The morphology and stability of the microfibers were studied. The release profile showed that it was possible to control the release rate of Dex from microfibers changing the salt concentration of the coagulating bath. The results indicated that HA-EDA-C18 microfibers are potentially useful for drug delivery applications.
Jae-seong Shim - One of the best experts on this subject based on the ideXlab platform.
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Mussel-Inspired Hyaluronic Acid Derivative Nanostructures for Improved Tumor Targeting and Penetration
ACS applied materials & interfaces, 2017Co-Authors: Song Yi Lee, Ju-hwan Park, Jae-seong Shim, Dae-duk Kim, Hyun-jong ChoAbstract:An amphiphilic Hyaluronic Acid-ceramide-dopamine (HACE-d) conjugate was prepared, and HACE-d-based nanoparticles (NPs) including phloretin (as an inhibitor of glucose transporter (GLUT1)) were fabricated. Mussel-inspired property of d was introduced to HACE NPs, and it may improve tumor targetability and penetration in addition to passive (based on enhanced permeability and retention effect) and active (interaction between HA and CD44 receptor) tumor targeting effects. HACE-d/phloretin NPs with 279 nm mean diameter, ∼0.2 polydispersity index, and −18 mV zeta potential were successfully fabricated, and a sustained drug release pattern was observed. HACE-d/phloretin NPs exhibited enhanced cellular accumulation efficiency and antiproliferation property, compared with HACE/phloretin NPs, in MDA-MB-231 cells (GLUT1 and CD44 receptor-expressed human breast adenocarcinoma cells). In a MDA-MB-231 spheroid model, HACE-d NPs group showed better tumor penetration efficiency and spheroid growth inhibitory effect rath...
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Boronic Acid-tethered amphiphilic Hyaluronic Acid Derivative-based nanoassemblies for tumor targeting and penetration.
Acta biomaterialia, 2017Co-Authors: Jae Young Jeong, Jae Young Lee, Jae-seong Shim, Song Yi Lee, Eun-hye Hong, Jae-hyoung Song, Sunghwa Choe, Dae-duk KimAbstract:(3-Aminomethylphenyl)boronic Acid (AMPB)-installed Hyaluronic Acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic Acid group of Hyaluronic Acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic Acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic Acid-sialic Acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic Acid-sialic Acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic Acid (AMPB)-tethered Hyaluronic Acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic Acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous milieu) may react with the sialic Acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic Acid-sialic Acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery
Colloids and surfaces. B Biointerfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery B Biointerfaces
Colloids and Surfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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nanocomplexes based on amphiphilic Hyaluronic Acid Derivative and polyethylene glycol lipid for ginsenoside rg3 delivery
Journal of Pharmaceutical Sciences, 2014Co-Authors: Jae Young Lee, Hyun-jong Cho, Jae-seong Shim, In-soo Yoon, Heejung Yang, Sangbum Kim, Sang Hyun Sung, Dae-duk KimAbstract:Hybrid nanocomplex formulations, based on amphiphilic Hyaluronic Acid–ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents.
Jae Young Lee - One of the best experts on this subject based on the ideXlab platform.
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Boronic Acid-tethered amphiphilic Hyaluronic Acid Derivative-based nanoassemblies for tumor targeting and penetration.
Acta biomaterialia, 2017Co-Authors: Jae Young Jeong, Jae Young Lee, Jae-seong Shim, Song Yi Lee, Eun-hye Hong, Jae-hyoung Song, Sunghwa Choe, Dae-duk KimAbstract:(3-Aminomethylphenyl)boronic Acid (AMPB)-installed Hyaluronic Acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic Acid group of Hyaluronic Acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic Acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic Acid-sialic Acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic Acid-sialic Acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic Acid (AMPB)-tethered Hyaluronic Acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic Acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous milieu) may react with the sialic Acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic Acid-sialic Acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery
Colloids and surfaces. B Biointerfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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Electrosprayed nanocomposites based on Hyaluronic Acid Derivative and Soluplus for tumor-targeted drug delivery B Biointerfaces
Colloids and Surfaces, 2016Co-Authors: Song Yi Lee, Ju-hwan Park, Jae Young Lee, Jae-seong Shim, Dae-duk Kim, Jeong-jun Lee, Jongkook Lee, Moon Young Heo, Hyun-jong ChoAbstract:Nanocomposite (NC) based on Hyaluronic Acid-ceramide (HACE) and Soluplus (SP) was fabricated by electrospraying for the tumor-targeted delivery of resveratrol (RSV). Amphiphilic property of both HACE and SP has been used to entrap RSV in the internal cavity of NC. Electrospraying with established experimental conditions produced HACE/SP/RSV NC with 230nm mean diameter, narrow size distribution, negative zeta potential, and >80% drug entrapment efficiency. Sustained and pH-dependent drug release profiles were observed in drug release test. Cellular uptake efficiency of HACE/SP NC was higher than that of SP NC, mainly based on HA-CD44 receptor interaction, in MDA-MB-231 (CD44 receptor-positive human breast cancer) cells. Selective tumor targetability of HACE/SP NC, compared to SP NC, was also confirmed in MDA-MB-231 tumor-xenograted mouse model using a near-infrared fluorescence (NIRF) imaging. According to the results of pharmacokinetic study in rats, decreased in vivo clearance and increased half-life of RSV in NC group, compared to drug solution group, were shown. Given that these experimental results, developed HACE/SP NC can be a promising theranostic nanosystem for CD44 receptor-expressed cancers.
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nanocomplexes based on amphiphilic Hyaluronic Acid Derivative and polyethylene glycol lipid for ginsenoside rg3 delivery
Journal of Pharmaceutical Sciences, 2014Co-Authors: Jae Young Lee, Hyun-jong Cho, Jae-seong Shim, In-soo Yoon, Heejung Yang, Sangbum Kim, Sang Hyun Sung, Dae-duk KimAbstract:Hybrid nanocomplex formulations, based on amphiphilic Hyaluronic Acid–ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents.
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Nanocomplexes Based on Amphiphilic Hyaluronic Acid Derivative and Polyethylene Glycol–Lipid for Ginsenoside Rg3 Delivery
Journal of pharmaceutical sciences, 2014Co-Authors: Jae Young Lee, Hyun-jong Cho, Jae-seong Shim, In-soo Yoon, Heejung Yang, Sangbum Kim, Sang Hyun Sung, Dae-duk KimAbstract:Hybrid nanocomplex formulations, based on amphiphilic Hyaluronic Acid–ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents.
