Intracellular Drug Delivery

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Xuesi Chen - One of the best experts on this subject based on the ideXlab platform.

  • one step synthesis of targeted acid labile polysaccharide proDrug for efficiently Intracellular Drug Delivery
    ACS Biomaterials Science & Engineering, 2018
    Co-Authors: Xiangru Feng, Jianxun Ding, Li Chen, Xuesi Chen
    Abstract:

    The therapeutic potential of the active targeting and acid-sensitive polysaccharide proDrug was investigated. The active targeting of polysaccharide proDrug was based on the specific interaction between cyclo(Arg-Gly-Asp-d-Phe-Lys) peptide (c(RGDfK)) and its receptor αvβ3 integrin overexpressed on the membrane of tumor cells. The cRGD-modified doxorubicin-conjugated hydroxyethyl starch (HES=DOX/cRGD) was synthesized via a one-step Schiff base reaction between oxidized HES, and DOX and c(RGDfK) that achieved an acid-accelerated Drug release profile. The targeted polysaccharide proDrug self-assembled into micelle in aqueous environment with a moderate hydrodynamic diameter of 77.1 nm. All data in vitro indicated enhanced cell uptake and elevated cytotoxicity of HES=DOX/cRGD toward human malignant melanoma A375 cells compared with HES=DOX and DOX. Moreover, the smart proDrug also exhibited upregulated accumulation in the tumor, improved antitumor efficacy, and reduced systemic cytotoxicity in vivo. The cRGD-...

  • polyion complex micelles with gradient ph sensitivity for adjustable Intracellular Drug Delivery
    Polymer Chemistry, 2015
    Co-Authors: Jinjin Chen, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Ying Zhang, Xuesi Chen
    Abstract:

    A series of poly(amino acid)-containing copolymers with gradient pH-sensitive side groups were synthesized through ring-opening reaction of succinic anhydride (SA), cis-cyclohexene-1,2-dicarboxylic anhydride (CDA), cis-aconitic anhydride (CA), and dimethylmaleic anhydride (DMMA) initiated by the amino groups in methoxy poly(ethylene glycol)-block-poly(L-lysine). Subsequently, four pH-responsive polyion complex (PIC) micelles (denoted as SAD, CDAD, CAD and DMMAD) were prepared through the electrostatic interaction between pH-responsive negatively charged copolymers and positively charged doxorubicin for adjustable Intracellular Drug Delivery. Due to the differences among the acid-sensitive side amide bonds, these micelles were proved to have gradient pH-sensitivity in the following order: SAD < CDAD < CAD < DMMAD. The in vitro Drug release rate was consistent with the sensitivity order of the micelles. The Intracellular DOX release behaviors and cytotoxicities of the PIC micelles could also be adjusted by the sensitivities of copolymers. All these different characters among the PIC micelles would be further applied for “on demand” Intracellular targeting chemotherapy in clinics.

  • dual responsive supramolecular nanogels for Intracellular Drug Delivery
    Chemical Communications, 2014
    Co-Authors: Xiaofei Chen, Zhe Zhang, Li Chen, Xuemei Yao, Jingping Zhang, Xuesi Chen
    Abstract:

    Supramolecular nanogels cross-linked by host–guest interaction between dextran grafted benzimidazole (Dex-g-BM) and thiol-β-cyclodextrin were designed. Their special supramolecular pH-sensitivity under acidic conditions (pH < 6, within the range of malignant cellular endosomes) and reduction sensitivity in response to biologically relevant stimuli will be of great advantage to the future of cancer chemotherapeutics.

  • redox sensitive shell crosslinked polypeptide block polysaccharide micelles for efficient Intracellular anticancer Drug Delivery
    Macromolecular Bioscience, 2013
    Co-Authors: Aiping Zhang, Zhe Zhang, Fenghua Shi, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Li Chen, Xuesi Chen
    Abstract:

    Redox-responsive SCMs based on amphiphilic PBLG-b-dextran with good biocompatibility are synthesized and used for efficient Intracellular Drug Delivery. The molecular structures and SCMs characteristics are characterized by (1) H NMR, FT-IR, TEM, and DLS. The hydrodynamic radius of SCMs increases gradually in PBS due to the cleavage of disulfide bond in micellar shell caused by the presence of GSH. The encapsulation efficiency and release kinetics of DOX are investigated. The fastest DOX release is observed under Intracellular-mimicking reductive environments. An MTT assay demonstrates that DOX-loaded SCMs show higher cellular proliferation inhibition against GSH-OEt pretreated HeLa and HepG2 than that of the non-pretreated and BSO-pretreated ones.

  • disulfide crosslinked pegylated starch micelles as efficient Intracellular Drug Delivery platforms
    Soft Matter, 2013
    Co-Authors: Aiping Zhang, Zhe Zhang, Fenghua Shi, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Li Chen, Xuesi Chen
    Abstract:

    Novel reduction-responsive disulfide core-crosslinked micelles based on amphiphilic starch-graft-poly(ethylene glycol) (starch-g-PEG) were prepared and used for efficient Intracellular Drug Delivery. The starch-g-PEG copolymers can be conveniently prepared by grafting starch with carboxyl group terminated PEG, and subsequently conjugated with lipoic acid for disulfide crosslinking. The self-assembled starch-g-PEG micelles and the corresponding disulfide core-crosslinked micelles were then characterized by transmission electron microscopy, dynamic laser scattering and fluorescence techniques. It is interesting to observe that the hydrodynamic radii of disulfide core-crosslinked micelles would increase gradually in phosphate buffered saline (PBS) due to the cleavage of the disulfide bond in the micellar core, caused by the presence of reductive glutathione (GSH). The glutathione-responsive behaviors of the disulfide core-crosslinked micelles should be attractive for Intracellular Drug Delivery. Thus, a model anticancer Drug doxorubicin (DOX) was loaded into micelles and the in vitro Drug release in response to GSH was also studied. The results showed that only a small amount of loaded DOX was released from the core-crosslinked starch-g-PEG micelles in PBS solution without GSH, while quick release occurred in the presence of 10.0 mM GSH. Confocal laser scanning microscopy and flow cytometry analyses further demonstrate that the disulfide crosslinked micelles exhibited a faster Drug release behavior in glutathione monoester (GSH-OEt) pretreated HeLa cells than that in the nonpretreated and buthionine sulfoximine (BSO) pretreated cells. In addition, the DOX-loaded crosslinked micelles show higher cellular proliferation inhibition against GSH-OEt pretreated HeLa and HepG2 than against the nonpretreated and BSO pretreated ones. These results suggest that such disulfide crosslinked starch-g-PEG micelles, which can efficiently release the loading Drug in response to Intracellular GSH concentration, may provide favorable platforms for cancer therapy.

Hongwei Duan - One of the best experts on this subject based on the ideXlab platform.

  • self assembled plasmonic vesicles of sers encoded amphiphilic gold nanoparticles for cancer cell targeting and traceable Intracellular Drug Delivery
    Journal of the American Chemical Society, 2012
    Co-Authors: Jibin Song, Jiajing Zhou, Hongwei Duan
    Abstract:

    We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted Drug Delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as Delivery carriers for anticancer Drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor Intracellular Drug Delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic Intracellular compartments, allows for triggered Intracellular Drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serv...

  • self assembled plasmonic vesicles of sers encoded amphiphilic gold nanoparticles for cancer cell targeting and traceable Intracellular Drug Delivery
    Journal of the American Chemical Society, 2012
    Co-Authors: Jibin Song, Jiajing Zhou, Hongwei Duan
    Abstract:

    We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted Drug Delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as Delivery carriers for anticancer Drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor Intracellular Drug Delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic Intracellular compartments, allows for triggered Intracellular Drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents.

Xiuli Zhuang - One of the best experts on this subject based on the ideXlab platform.

  • core cross linked poly ethylene glycol graft dextran nanoparticles for reduction and ph dual responsive Intracellular Drug Delivery
    Journal of Colloid and Interface Science, 2017
    Co-Authors: Hua Lian, Chunsheng Xiao, Xin Chen, Lijie Duan, Guanghui Gao, Xiuli Zhuang
    Abstract:

    A kind of core cross-linked poly(ethylene glycol)-graft-Dextran nanoparticles (CPD NPs) was prepared by a simple chemical cross-linking method for reduction and pH dual response Drug Delivery. The resultant CPD NPs are of homogeneous spherical structure with sizes from 69±11 to 107±18nm. Doxorubicin (DOX) was then loaded into the CPD NPs in high efficiency, and showing typical reduction and pH dual responsive release profiles. The flow cytometric analysis and confocal laser scanning microscopy (CLSM) confirmed that the DOX-loaded CPD NPs could be internalized into cancer cell efficiently and release DOX in Intracellular environment. Furthermore, cell cytotoxicity assays indicated that the CPD NPs had good biocompatibility toward both cancerous and normal cells, while the Dox-loaded CPD NPs exhibited significant inhibition of cell proliferation in various cancer cells. Therefore, this biocompatible CPD NP may have great potential for Intracellular Drug Delivery in clinical cancer therapy.

  • polyion complex micelles with gradient ph sensitivity for adjustable Intracellular Drug Delivery
    Polymer Chemistry, 2015
    Co-Authors: Jinjin Chen, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Ying Zhang, Xuesi Chen
    Abstract:

    A series of poly(amino acid)-containing copolymers with gradient pH-sensitive side groups were synthesized through ring-opening reaction of succinic anhydride (SA), cis-cyclohexene-1,2-dicarboxylic anhydride (CDA), cis-aconitic anhydride (CA), and dimethylmaleic anhydride (DMMA) initiated by the amino groups in methoxy poly(ethylene glycol)-block-poly(L-lysine). Subsequently, four pH-responsive polyion complex (PIC) micelles (denoted as SAD, CDAD, CAD and DMMAD) were prepared through the electrostatic interaction between pH-responsive negatively charged copolymers and positively charged doxorubicin for adjustable Intracellular Drug Delivery. Due to the differences among the acid-sensitive side amide bonds, these micelles were proved to have gradient pH-sensitivity in the following order: SAD < CDAD < CAD < DMMAD. The in vitro Drug release rate was consistent with the sensitivity order of the micelles. The Intracellular DOX release behaviors and cytotoxicities of the PIC micelles could also be adjusted by the sensitivities of copolymers. All these different characters among the PIC micelles would be further applied for “on demand” Intracellular targeting chemotherapy in clinics.

  • redox sensitive shell crosslinked polypeptide block polysaccharide micelles for efficient Intracellular anticancer Drug Delivery
    Macromolecular Bioscience, 2013
    Co-Authors: Aiping Zhang, Zhe Zhang, Fenghua Shi, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Li Chen, Xuesi Chen
    Abstract:

    Redox-responsive SCMs based on amphiphilic PBLG-b-dextran with good biocompatibility are synthesized and used for efficient Intracellular Drug Delivery. The molecular structures and SCMs characteristics are characterized by (1) H NMR, FT-IR, TEM, and DLS. The hydrodynamic radius of SCMs increases gradually in PBS due to the cleavage of disulfide bond in micellar shell caused by the presence of GSH. The encapsulation efficiency and release kinetics of DOX are investigated. The fastest DOX release is observed under Intracellular-mimicking reductive environments. An MTT assay demonstrates that DOX-loaded SCMs show higher cellular proliferation inhibition against GSH-OEt pretreated HeLa and HepG2 than that of the non-pretreated and BSO-pretreated ones.

  • disulfide crosslinked pegylated starch micelles as efficient Intracellular Drug Delivery platforms
    Soft Matter, 2013
    Co-Authors: Aiping Zhang, Zhe Zhang, Fenghua Shi, Jianxun Ding, Chunsheng Xiao, Xiuli Zhuang, Li Chen, Xuesi Chen
    Abstract:

    Novel reduction-responsive disulfide core-crosslinked micelles based on amphiphilic starch-graft-poly(ethylene glycol) (starch-g-PEG) were prepared and used for efficient Intracellular Drug Delivery. The starch-g-PEG copolymers can be conveniently prepared by grafting starch with carboxyl group terminated PEG, and subsequently conjugated with lipoic acid for disulfide crosslinking. The self-assembled starch-g-PEG micelles and the corresponding disulfide core-crosslinked micelles were then characterized by transmission electron microscopy, dynamic laser scattering and fluorescence techniques. It is interesting to observe that the hydrodynamic radii of disulfide core-crosslinked micelles would increase gradually in phosphate buffered saline (PBS) due to the cleavage of the disulfide bond in the micellar core, caused by the presence of reductive glutathione (GSH). The glutathione-responsive behaviors of the disulfide core-crosslinked micelles should be attractive for Intracellular Drug Delivery. Thus, a model anticancer Drug doxorubicin (DOX) was loaded into micelles and the in vitro Drug release in response to GSH was also studied. The results showed that only a small amount of loaded DOX was released from the core-crosslinked starch-g-PEG micelles in PBS solution without GSH, while quick release occurred in the presence of 10.0 mM GSH. Confocal laser scanning microscopy and flow cytometry analyses further demonstrate that the disulfide crosslinked micelles exhibited a faster Drug release behavior in glutathione monoester (GSH-OEt) pretreated HeLa cells than that in the nonpretreated and buthionine sulfoximine (BSO) pretreated cells. In addition, the DOX-loaded crosslinked micelles show higher cellular proliferation inhibition against GSH-OEt pretreated HeLa and HepG2 than against the nonpretreated and BSO pretreated ones. These results suggest that such disulfide crosslinked starch-g-PEG micelles, which can efficiently release the loading Drug in response to Intracellular GSH concentration, may provide favorable platforms for cancer therapy.

  • ph and reduction dual responsive polyurethane triblock copolymers for efficient Intracellular Drug Delivery
    Soft Matter, 2013
    Co-Authors: Jianxun Ding, Xiuli Zhuang, Yilong Cheng, Wantong Song, Xuesi Chen
    Abstract:

    A series of pH/reduction dual responsive poly(ethylene glycol)/polyurethane triblock copolymers containing tertiary amines and disulfide bonds are reported. The polyurethane block copolymers self-assembled into stable micelles in aqueous medium at pH 7.4, which responded rapidly to both a narrow pH change within the physiologically relevant pH range and a reduction environment mimicking the Intracellular space. The in vitro Drug release from doxorubicin (DOX)-loaded polyurethane micelles was significantly accelerated by reducing the pH or by addition of an Intracellular reducing agent, glutathione (GSH). Confocal laser scanning microscopy (CLSM) and flow cytometry measurements revealed that the Intracellular Drug release from the DOX-loaded nanoparticles was increased in the HeLa cells with enhanced Intracellular GSH level. In addition, even though the polyurethane block copolymers exhibited good cytocompatibility, the DOX-loaded polyurethane micelles displayed efficient growth inhibition of HeLa and HepG2 cells, which showed a dependence on the Intracellular GSH concentration. Owing to their unique responsiveness to dual biological stimuli, the biocompatible and bioreducible polyurethane block copolymers have the potential to serve as a versatile platform for Intracellular Drug Delivery.

Frank Caruso - One of the best experts on this subject based on the ideXlab platform.

  • templated assembly of ph labile polymer Drug particles for Intracellular Drug Delivery
    Advanced Functional Materials, 2012
    Co-Authors: Jiwei Cui, Yan Yan, Yajun Wang, Frank Caruso
    Abstract:

    The preparation of pH-labile polymer-Drug particles via mesoporous silica-templated assembly for anticancer Drug Delivery into cancer cells is reported. The polymer-Drug conjugate is synthesized via thiol-maleimide click chemistry using thiolated poly(methacrylic acid) (PMASH) and a pH-labile doxorubicin (Dox) derivative. Drug-loaded polymer particles that are stable under physiological conditions are obtained through infiltration of the conjugates into mesoporous silica particles, followed by cross-linking the PMASH chains, and subsequent removal of the porous silica templates. The encapsulated Dox is released from the particles through cleavage of the hydrazone bonds between Dox and PMASH at endosomal/lysosomal pH. Cell viability assays show that the assembled PMASH particles have negligible cytotoxicity to LIM1899 human colorectal cancer cells. In comparison, Dox-loaded PMASH particles cause significant cell death following internalization. The reported particles represent a novel and versatile class of stimuli-responsive carriers for controlled Drug Delivery.

  • immobilization and Intracellular Delivery of an anticancer Drug using mussel inspired polydopamine capsules
    Biomacromolecules, 2012
    Co-Authors: Jiwei Cui, Yan Yan, Georgina K Such, Kang Liang, Christopher J Ochs, Almar Postma, Frank Caruso
    Abstract:

    We report a facile approach to immobilize pH-cleavable polymer-Drug conjugates in mussel-inspired polydopamine (PDA) capsules for Intracellular Drug Delivery. Our design takes advantage of the faci...

  • encapsulation of water insoluble Drugs in polymer capsules prepared using mesoporous silica templates for Intracellular Drug Delivery
    Advanced Materials, 2010
    Co-Authors: Yajun Wang, Jiwei Cui, Yan Yan, Leticia Hostarigau, Joan K Heath, Edouard C Nice, Frank Caruso
    Abstract:

    More than 40% of active compounds identifi ed through screening of combinatorial libraries are poorly water-soluble, rendering them unsuitable for further Drug development because of diffi culties associated with their Delivery using conventional formulation techniques. [ 1 ] Nanoparticles can act as Drug carriers for waterinsoluble cargo and this has become an important emerging area of nanotechnology. [ 2 ] As many potent anticancer agents are hydrophobic molecules, the development of nanomaterials for delivering such Drugs has received signifi cant attention. Mesoporous silica (MS) particles are attractive as potential Drug Delivery systems due to their high surface area (up to ∼ 1500 m 2 g − 1 ), controllable pore size ( ∼ 2–50 nm) and pore structure, and tunable size ( ∼ 60 nm − 10 μ m) and morphology. [ 3 ]

  • encapsulation of water insoluble Drugs in polymer capsules prepared using mesoporous silica templates for Intracellular Drug Delivery
    Advanced Materials, 2010
    Co-Authors: Yajun Wang, Jiwei Cui, Yan Yan, Leticia Hostarigau, Joan K Heath, Edouard C Nice, Frank Caruso
    Abstract:

    Water-insoluble compounds were encapsulated in polymer capsules through mesoporous silica nanoparticle-mediated layer-by-layer assembly. The Drug-loaded capsules exhibit excellent colloidal stability and high potency to colorectal cancer cells in vitro with similar cytotoxicity to the free Drug dissolved in organic solvent. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Jun Wang - One of the best experts on this subject based on the ideXlab platform.

  • dually responsive mesoporous silica nanoparticles regulated by upper critical solution temperature polymers for Intracellular Drug Delivery
    Journal of Materials Chemistry B, 2017
    Co-Authors: Mingyang Hei, Jun Wang, Kelly Wang, Weiping Zhu, Peter X
    Abstract:

    We synthesized a new type of upper critical solution temperature (UCST) thermally responsive polymers (TRPs) with varying responsive temperatures (cloud points). We then grafted one of the TRPs with a cloud point of 42°C on the surface of mesoporous silica nanoparticles (MSN) using disulfide bonds to achieve a novel, dual responsive release system. With this system, the cargo release profiles are responsive to both temperature and reducing agents. When loaded with doxorubicin hydrochloride (DOX), the system could deliver DOX into breast cancer cells (SK-BR-3) in a controlled fashion and present high toxicity.

  • doxorubicin tethered responsive gold nanoparticles facilitate Intracellular Drug Delivery for overcoming multiDrug resistance in cancer cells
    ACS Nano, 2011
    Co-Authors: Feng Wang, Yucai Wang, Menghua Xiong, Jun Wang
    Abstract:

    MultiDrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Through the development of a Drug Delivery system that tethers doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an acid-labile linkage (DOX-Hyd@AuNPs), we have demonstrated that multiDrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and a responsive Intracellular release of doxorubicin from the gold nanoparticles in acidic organelles. DOX-Hyd@AuNPs achieved enhanced Drug accumulation and retention in multiDrug resistant MCF-7/ADR cancer cells when it was compared with free doxorubicin. It released doxorubicin in response to the pH of acidic organelles following endocytosis, opposite to the noneffective Drug release from doxorubicin-tethered gold nanoparticles via the carbamate linkage (DOX-Cbm@AuNPs), which was shown by the recovered fluorescence of doxorubicin from quenching due to the nanosurface energy transfer ...

  • core shell corona micelle stabilized by reversible cross linkage for Intracellular Drug Delivery
    Macromolecular Rapid Communications, 2010
    Co-Authors: Yucai Wang, Menghua Xiong, Tianmeng Sun, Yi Yan Yang, Jun Wang
    Abstract:

    Reversibly cross-linked core-shell-corona micelles based on a triblock copolymer composed of poly(aliphatic ester), polyphosphoester, and poly(ethylene glycol) are reported. The triblock copolymer is synthesized through consecutive ring-opening polymerization of e-caprolactone and 2,4-dinitrophenylthioethyl ethylene phosphate, followed by conjugation of poly(ethylene glycol). After deprotection under mild conditions, the amphiphilic polymer forms core-shell-corona micelles with free thiols in the shell. Cross-linking of the micelles within the shell reduces their critical micellization concentration and enhances their stability against severe conditions. The redox-sensitive cross-linkage allows the facilitated release of entrapped anticancer Drugs in the cytoplasm in response to the Intracellular reductive environment. With enhanced stability during circulation after administration, and accelerated Intracellular Drug release at the target site, the biocompatible and biodegradable shell-cross-linked polymeric micelle is promising as a Drug vehicle for cancer chemotherapy.

  • shell detachable micelles based on disulfide linked block copolymer as potential carrier for Intracellular Drug Delivery
    Bioconjugate Chemistry, 2009
    Co-Authors: Lingyan Tang, Yucai Wang, Jun Wang
    Abstract:

    Aiming at development of a micellar nanoparticle system for Intracellular Drug release triggered by glutathione in tumor cells, a disulfide-linked biodegradable diblock copolymer of poly(e-caprolactone) and poly(ethyl ethylene phosphate) was synthesized. It formed biocompatible micelles loaded with doxorubicin in aqueous solution but detached the shell material under glutathione stimulus, resulting in rapid Drug release with destruction of micellar structure. These glutathione-sensitive micelles also rapidly released the Drug molecules Intracellularly and led to enhanced growth inhibition to A549 tumor cells, suggesting that this nanoparticle system may have potential for improving Drug Delivery efficacy.