Absorption Barrier

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Yuan Huang - One of the best experts on this subject based on the ideXlab platform.

  • sub 50 nm nanoparticles with biomimetic surfaces to sequentially overcome the mucosal diffusion Barrier and the epithelial Absorption Barrier
    Advanced Functional Materials, 2016
    Co-Authors: Jun Wu, Wei Shan, Zhou Zhou, Yuan Huang
    Abstract:

    Although nanoparticles (NPs) have been used for many drug delivery applications, oral Absorption of NPs has remained a big challenge. NPs for oral delivery of biotherapeutics have to penetrate both the diffusion Barrier of the mucus and the Absorption Barrier of the epithelium. This creates an obstacle for developing an effective NP platform for oral delivery because overcoming these two Barriers requires different or even contradictory surface properties. Inspired by the features of some viruses, this study reports the development of a unique sub-50 nm polymeric NP platform that possesses a large amount of targeting ligands anchored on the surface while being moderately concealed under a “muco-inert” shield. NP library screening demonstrates a strong correlation between the relative lengths of the surface components and NP behavior on mucosal tissue. When a balance is obtained regarding optimal shielding of ligands, the NPs exhibit both excellent mucus permeation and transepithelial transport, and are efficiently absorbed into systemic circulation. Insulin-loaded NPs as a model oral therapy for diabetes generates a hypoglycemic response on diabetic animals following oral administration. This study demonstrates the great potency of a NP platform that exhibits an affinity balance between mucus and epithelium in facilitating the oral delivery of biotherapeutics.

  • Sub‐50 nm Nanoparticles with Biomimetic Surfaces to Sequentially Overcome the Mucosal Diffusion Barrier and the Epithelial Absorption Barrier
    Advanced Functional Materials, 2016
    Co-Authors: Jun Wu, Wei Shan, Zhou Zhou, Yuan Huang
    Abstract:

    Although nanoparticles (NPs) have been used for many drug delivery applications, oral Absorption of NPs has remained a big challenge. NPs for oral delivery of biotherapeutics have to penetrate both the diffusion Barrier of the mucus and the Absorption Barrier of the epithelium. This creates an obstacle for developing an effective NP platform for oral delivery because overcoming these two Barriers requires different or even contradictory surface properties. Inspired by the features of some viruses, this study reports the development of a unique sub-50 nm polymeric NP platform that possesses a large amount of targeting ligands anchored on the surface while being moderately concealed under a “muco-inert” shield. NP library screening demonstrates a strong correlation between the relative lengths of the surface components and NP behavior on mucosal tissue. When a balance is obtained regarding optimal shielding of ligands, the NPs exhibit both excellent mucus permeation and transepithelial transport, and are efficiently absorbed into systemic circulation. Insulin-loaded NPs as a model oral therapy for diabetes generates a hypoglycemic response on diabetic animals following oral administration. This study demonstrates the great potency of a NP platform that exhibits an affinity balance between mucus and epithelium in facilitating the oral delivery of biotherapeutics.

  • overcoming the diffusion Barrier of mucus and Absorption Barrier of epithelium by self assembled nanoparticles for oral delivery of insulin
    ACS Nano, 2015
    Co-Authors: Wei Shan, Lian Li, Jiaju Zhong, Zhirong Zhang, Yuan Huang
    Abstract:

    Nanoparticles (NPs) have demonstrated great potential for the oral delivery of protein drugs that have very limited oral bioavailability. Orally administered NPs could be absorbed by the epithelial tissue only if they successfully permeate through the mucus that covers the epithelium. However, efficient epithelial Absorption and mucus permeation require very different surface properties of a nanocarrier. We herein report self-assembled NPs for efficient oral delivery of insulin by facilitating both of these two processes. The NPs possess a nanocomplex core composed of insulin and cell penetrating peptide (CPP), and a dissociable hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivatives. After systematic screening using mucus-secreting epithelial cells, NPs exhibit excellent permeation in mucus due to the “mucus-inert” pHPMA coating, as well as high epithelial Absorption mediated by CPP. The investigation of NP behavior shows that the pHPMA molecules gradually dissociate from ...

Wei Shan - One of the best experts on this subject based on the ideXlab platform.

  • sub 50 nm nanoparticles with biomimetic surfaces to sequentially overcome the mucosal diffusion Barrier and the epithelial Absorption Barrier
    Advanced Functional Materials, 2016
    Co-Authors: Jun Wu, Wei Shan, Zhou Zhou, Yuan Huang
    Abstract:

    Although nanoparticles (NPs) have been used for many drug delivery applications, oral Absorption of NPs has remained a big challenge. NPs for oral delivery of biotherapeutics have to penetrate both the diffusion Barrier of the mucus and the Absorption Barrier of the epithelium. This creates an obstacle for developing an effective NP platform for oral delivery because overcoming these two Barriers requires different or even contradictory surface properties. Inspired by the features of some viruses, this study reports the development of a unique sub-50 nm polymeric NP platform that possesses a large amount of targeting ligands anchored on the surface while being moderately concealed under a “muco-inert” shield. NP library screening demonstrates a strong correlation between the relative lengths of the surface components and NP behavior on mucosal tissue. When a balance is obtained regarding optimal shielding of ligands, the NPs exhibit both excellent mucus permeation and transepithelial transport, and are efficiently absorbed into systemic circulation. Insulin-loaded NPs as a model oral therapy for diabetes generates a hypoglycemic response on diabetic animals following oral administration. This study demonstrates the great potency of a NP platform that exhibits an affinity balance between mucus and epithelium in facilitating the oral delivery of biotherapeutics.

  • Sub‐50 nm Nanoparticles with Biomimetic Surfaces to Sequentially Overcome the Mucosal Diffusion Barrier and the Epithelial Absorption Barrier
    Advanced Functional Materials, 2016
    Co-Authors: Jun Wu, Wei Shan, Zhou Zhou, Yuan Huang
    Abstract:

    Although nanoparticles (NPs) have been used for many drug delivery applications, oral Absorption of NPs has remained a big challenge. NPs for oral delivery of biotherapeutics have to penetrate both the diffusion Barrier of the mucus and the Absorption Barrier of the epithelium. This creates an obstacle for developing an effective NP platform for oral delivery because overcoming these two Barriers requires different or even contradictory surface properties. Inspired by the features of some viruses, this study reports the development of a unique sub-50 nm polymeric NP platform that possesses a large amount of targeting ligands anchored on the surface while being moderately concealed under a “muco-inert” shield. NP library screening demonstrates a strong correlation between the relative lengths of the surface components and NP behavior on mucosal tissue. When a balance is obtained regarding optimal shielding of ligands, the NPs exhibit both excellent mucus permeation and transepithelial transport, and are efficiently absorbed into systemic circulation. Insulin-loaded NPs as a model oral therapy for diabetes generates a hypoglycemic response on diabetic animals following oral administration. This study demonstrates the great potency of a NP platform that exhibits an affinity balance between mucus and epithelium in facilitating the oral delivery of biotherapeutics.

  • overcoming the diffusion Barrier of mucus and Absorption Barrier of epithelium by self assembled nanoparticles for oral delivery of insulin
    ACS Nano, 2015
    Co-Authors: Wei Shan, Lian Li, Jiaju Zhong, Zhirong Zhang, Yuan Huang
    Abstract:

    Nanoparticles (NPs) have demonstrated great potential for the oral delivery of protein drugs that have very limited oral bioavailability. Orally administered NPs could be absorbed by the epithelial tissue only if they successfully permeate through the mucus that covers the epithelium. However, efficient epithelial Absorption and mucus permeation require very different surface properties of a nanocarrier. We herein report self-assembled NPs for efficient oral delivery of insulin by facilitating both of these two processes. The NPs possess a nanocomplex core composed of insulin and cell penetrating peptide (CPP), and a dissociable hydrophilic coating of N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) derivatives. After systematic screening using mucus-secreting epithelial cells, NPs exhibit excellent permeation in mucus due to the “mucus-inert” pHPMA coating, as well as high epithelial Absorption mediated by CPP. The investigation of NP behavior shows that the pHPMA molecules gradually dissociate from ...

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

  • Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand.
    Nano Letters, 2018
    Co-Authors: Yixuan Tang, Xiaoyou Wang, Kexin Huang, Liting Cheng, Jing Zhou, Yang Yu, Shuang Wu, Zhangbao Chen
    Abstract:

    Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral Absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic-co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral Absorption Barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performe...

  • Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand
    Nano Letters, 2018
    Co-Authors: Yixuan Tang, Jiaqi Lin, Xiaoyou Wang, Kexin Huang, Jing Xie, Liting Cheng, Jing Zhou, Yang Yu, Shuang Wu, Zhangbao Chen
    Abstract:

    Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral Absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic-co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral Absorption Barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections. © 2018 American Chemical Society.

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

  • sub 50 nm nanoparticles with biomimetic surfaces to sequentially overcome the mucosal diffusion Barrier and the epithelial Absorption Barrier
    Advanced Functional Materials, 2016
    Co-Authors: Jun Wu, Wei Shan, Zhou Zhou, Yuan Huang
    Abstract:

    Although nanoparticles (NPs) have been used for many drug delivery applications, oral Absorption of NPs has remained a big challenge. NPs for oral delivery of biotherapeutics have to penetrate both the diffusion Barrier of the mucus and the Absorption Barrier of the epithelium. This creates an obstacle for developing an effective NP platform for oral delivery because overcoming these two Barriers requires different or even contradictory surface properties. Inspired by the features of some viruses, this study reports the development of a unique sub-50 nm polymeric NP platform that possesses a large amount of targeting ligands anchored on the surface while being moderately concealed under a “muco-inert” shield. NP library screening demonstrates a strong correlation between the relative lengths of the surface components and NP behavior on mucosal tissue. When a balance is obtained regarding optimal shielding of ligands, the NPs exhibit both excellent mucus permeation and transepithelial transport, and are efficiently absorbed into systemic circulation. Insulin-loaded NPs as a model oral therapy for diabetes generates a hypoglycemic response on diabetic animals following oral administration. This study demonstrates the great potency of a NP platform that exhibits an affinity balance between mucus and epithelium in facilitating the oral delivery of biotherapeutics.

  • Sub‐50 nm Nanoparticles with Biomimetic Surfaces to Sequentially Overcome the Mucosal Diffusion Barrier and the Epithelial Absorption Barrier
    Advanced Functional Materials, 2016
    Co-Authors: Jun Wu, Wei Shan, Zhou Zhou, Yuan Huang
    Abstract:

    Although nanoparticles (NPs) have been used for many drug delivery applications, oral Absorption of NPs has remained a big challenge. NPs for oral delivery of biotherapeutics have to penetrate both the diffusion Barrier of the mucus and the Absorption Barrier of the epithelium. This creates an obstacle for developing an effective NP platform for oral delivery because overcoming these two Barriers requires different or even contradictory surface properties. Inspired by the features of some viruses, this study reports the development of a unique sub-50 nm polymeric NP platform that possesses a large amount of targeting ligands anchored on the surface while being moderately concealed under a “muco-inert” shield. NP library screening demonstrates a strong correlation between the relative lengths of the surface components and NP behavior on mucosal tissue. When a balance is obtained regarding optimal shielding of ligands, the NPs exhibit both excellent mucus permeation and transepithelial transport, and are efficiently absorbed into systemic circulation. Insulin-loaded NPs as a model oral therapy for diabetes generates a hypoglycemic response on diabetic animals following oral administration. This study demonstrates the great potency of a NP platform that exhibits an affinity balance between mucus and epithelium in facilitating the oral delivery of biotherapeutics.

Yixuan Tang - One of the best experts on this subject based on the ideXlab platform.

  • Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand.
    Nano Letters, 2018
    Co-Authors: Yixuan Tang, Xiaoyou Wang, Kexin Huang, Liting Cheng, Jing Zhou, Yang Yu, Shuang Wu, Zhangbao Chen
    Abstract:

    Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral Absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic-co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral Absorption Barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performe...

  • Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand
    Nano Letters, 2018
    Co-Authors: Yixuan Tang, Jiaqi Lin, Xiaoyou Wang, Kexin Huang, Jing Xie, Liting Cheng, Jing Zhou, Yang Yu, Shuang Wu, Zhangbao Chen
    Abstract:

    Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral Absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic-co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral Absorption Barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections. © 2018 American Chemical Society.