Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids

Subedi, Laxman; Pandey, Prashant; Khadka, Bikram; Shim, Jung‐Hyun; Cho, Seung‐Sik; Kweon, Seho; Byun, Youngro; Kim, Ki-Taek; Park, Jin Woo

doi:10.1080/10717544.2022.2149896

Cited by 8 publications

(5 citation statements)

References 53 publications

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“…Next, Subedi el al. have developed ATV-loaded nanoemulsions (ATV-NEs) with targeting multivalent intestinal transporters to increase the oral bioavailability of ATV . To enable bile-acid- and multivitamin-transporter-mediated permeation of ATV without P-glycoprotein (P-gp)-mediated efflux, ATV-NEs were produced by oil-in-water emulsification for transporter-targeted delivery.…”

Section: Advanced Applications Of Modular Multivalent Nanobioconjugatesmentioning

confidence: 99%

“…have developed ATV-loaded nanoemulsions (ATV-NEs) with targeting multivalent intestinal transporters to increase the oral bioavailability of ATV. 121 To enable bileacid-and multivitamin-transporter-mediated permeation of ATV without P-glycoprotein (P-gp)-mediated efflux, ATV-NEs were produced by oil-in-water emulsification for transporter-targeted delivery. These anchors included an ionic complex of deoxycholic acid (DOCA) with the cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP), a biotin-conjugated lipid (Biotinyl PE), and d-alpha-tocopherol polyethylene glycol succinate (TPGS).…”

Section: Modular Multivalency Offers Brain Targeting Via Transcytosismentioning

confidence: 99%

“…These anchors included an ionic complex of deoxycholic acid (DOCA) with the cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP), a biotin-conjugated lipid (Biotinyl PE), and d-alpha-tocopherol polyethylene glycol succinate (TPGS). 121 Although multivalent interaction increases the binding ability, this multivalent interaction also depends on other factors like spatial arrangement of ligands, ligand density, and receptor density on the target cell surface, which varies with the type and stages of tumor. To study this effect, Zhang et al synthesized a citric acid-coated iron oxide nanoparticle which was conjugated to raltiterxed (RTX)-modified multivalent polyethylene amine ligand cluster PR n (n = 2,4,8), where RTX acted as a self-targeted anticancer agent.…”

Section: Modular Multivalency Offers Brain Targeting Via Transcytosismentioning

confidence: 99%

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Synthesis and Applications of Colloidal Nanobioconjugates with Modular Multivalency: A Review

Dalal,

Ray

2024

ACS Appl. Nano Mater.

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Nanobioconjugates are extensively employed in an array of biomedical applications, such as photodynamic therapy materials, drug delivery carriers, bioimaging probes, single molecule tracking, detection probes, and brain targeting agents through transcytosis. To provide these biological applications, nanoparticles need to be designed delicately with specific targeting ligands to recognize specific molecules or to target specific receptors over the cell’s surface, and this cellular internalization process generally follows a receptor-mediated endocytosis pathway. The variables that govern this interaction as well as the cellular entry/exit process are the size and shape of the nanoparticle, surface chemistry and surface charge of the nanoparticle, and nanoparticle multivalency (the number of targeting ligands on the nanoparticle surface). Herein, we elaborately discuss the nanoparticle multivalency parameter. Monovalent nanobioconjugates always interact with cell receptors through 1:1 interaction and reduce receptor clustering, which is inefficient for nanoparticle internalization. In the case of multivalent nanobioconjugates, this interaction occurs through multiple ligands from one nanoparticle with multiple receptors on the cell surface, which leads to receptor clustering. However, nanobioconjugates with uncontrolled multivalency reduce receptor mobility, followed by lysosomal trapping, and fail for proper biomedical applications. Therefore, the development of nanobioconjugates with modular or controlled multivalency is much more challenging and is also needed for different biomedical applications. Throughout this review, we describe the crucial role of nanoparticle multivalency in different biomedical applications. Next, we discuss various synthesis approaches to develop monovalent nanobioconjugates via a surface masking strategy and streptavidin–biotin interaction. Moreover, we discuss how nanoparticle multivalency can be controlled by using a competitor of targeting ligand, by regulating the size of the nanoparticle, and by changing the reaction medium/reaction condition. Next, we demonstrate how nanoparticle multivalency directs the cellular entry–exit mechanism, subcellular targeting, and brain targeting. Finally, we discuss the application and effect of multivalent nanobioconjugates in drug delivery, tumor targeting, single-molecule imaging, and detection of cancer cells/proteins/peptides.

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Section: Advanced Applications Of Modular Multivalent Nanobioconjugatesmentioning

confidence: 99%

Section: Modular Multivalency Offers Brain Targeting Via Transcytosismentioning

confidence: 99%

Section: Modular Multivalency Offers Brain Targeting Via Transcytosismentioning

confidence: 99%

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Synthesis and Applications of Colloidal Nanobioconjugates with Modular Multivalency: A Review

Dalal,

Ray

2024

ACS Appl. Nano Mater.

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“…The concept of the application of nanotechnology in disease treatment was proposed by Siddiqui and associates [46]. The utilization of nano-delivery systems to achieve cancer targeting has been proven to be an effective approach for obtaining better therapeutic outcomes [47][48][49]. As nanoparticles are able to bypass the natural barriers in the body, they can achieve effective release kinetics, and can easily target the desired locations [50,51].…”

Section: Pharmaceutical Application Of Flavonoids Against Various Can...mentioning

confidence: 99%

Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer

et al. 2023

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Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds’ anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid–lipid and liquid–lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies.

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“…Because they are highly expressed in the intestine, transporters such as peptide transporter 1, organic anion transporting polypeptides, and monocarboxylate transporter protein 1 are used for oral targeted delivery [ 39 – 41 ]. Above all, oral delivery systems using bile acids to target the apical sodium-dependent bile acid transporter (ASBT) have achieved significant improvements in the intestinal permeability of not only hydrophilic small-molecule anticancer drugs, but also macromolecules [ 42 , 43 ]. ASBT-mediated endocytosis occurs when bile acids specifically bind to ASBT, inducing a transformational change in the occluded state of ASBT and the formation of ASBT vesicles for endocytosis [ 32 , 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery

Kweon,

Lee,

Yang

et al. 2023

Biomater Res

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Background Despite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT). Methods In silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of mono-, bis-, and tetra-deoxycholic acid (DOCA) (monoDOCA, bisDOCA, and tetraDOCA) with ASBT. After synthesizing the chimeric GLP-1A-conjugated oligomeric DOCAs (mD-G1A, bD-G1A, and tD-G1A) using a maleimide reaction, in vitro cellular permeability and insulinotropic effects were assessed. Furthermore, in vivo oral absorption in rats and hypoglycemic effect on diabetic db/db mice model were evaluated. Results In silico results showed that tetraDOCA had the lowest interaction energy, indicating high binding affinity to ASBT. Insulinotropic effects of GLP-1A-conjugated oligomeric DOCAs were not different from those of GLP-1A-Cys or exenatide. Moreover, bD-G1A and tD-G1A exhibited improved in vitro Caco-2 cellular permeability and showed higher in vivo bioavailability (7.58% and 8.63%) after oral administration. Regarding hypoglycemic effects on db/db mice, tD-G1A (50 μg/kg) lowered the glucose level more than bD-G1A (50 μg/kg) compared with the control (35.5% vs. 26.4%). Conclusion GLP-1A was conjugated with oligomeric DOCAs, and the resulting chimeric compound showed the potential not only for glucagon-like peptide-1 receptor agonist activity but also for oral delivery. These findings suggest that oligomeric DOCAs can be used as effective carriers for oral delivery of GLP-1A, offering a promising solution for enhancing its oral bioavailability and improving diabetes treatment. Graphical Abstract

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Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids

Cited by 8 publications

References 53 publications

Synthesis and Applications of Colloidal Nanobioconjugates with Modular Multivalency: A Review

Synthesis and Applications of Colloidal Nanobioconjugates with Modular Multivalency: A Review

Exploring the Remarkable Chemotherapeutic Potential of Polyphenolic Antioxidants in Battling Various Forms of Cancer

Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery

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