A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis

Wu, Ya; Sun, Minghui; Wang, Dan; Li, Genyun; Huang, Jiangeng; Tan, Songwei; Bao, Lin; Li, Qian; Gao, Li; Si, Luqin

doi:10.1039/c9bm00925f

Cited by 45 publications

(21 citation statements)

References 50 publications

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“…Adrenomedullin (Ashizuka et al, 2013) Downregulation of inflammatory cytokines NA Tyr-Pro-D-Ala-NH2-DI-1 (Salaga et al, 2018) Regulate GLP-2 level Intracolonic as a part of the drug carrier. Wu et al (2019) developed a colonspecific delivery system-PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). In this study, KPV is utilized as a ligand for PepT1 to achieve targeting delivery.…”

Section: Therapeutic Peptidesmentioning

confidence: 99%

“…Different inflammatory markers can also be used as a target such as CD98, CD44, and folate and mannose receptor, all overexpressed on the surface of colon epithelial cells and macrophages and peptide transporter-1 (Pept1) to target macrophages ( Yang et al, 2020 ). Recently, hyaluronic acid has been used to selectively target CD44 ( Misra et al, 2015 ; Lee Y. et al, 2020 ) while lysine-proline-valine (KPV), a C-terminal peptide fragment of a α-melanocyte-stimulating hormone, can target Pept1 ( Wu et al, 2019 ).…”

Section: Oral Ibd Treatment Strategiesmentioning

confidence: 99%

“…In some studies, KPV was utilized as a part of the drug carrier. Wu et al (2019) developed a colon-specific delivery system—PLGA-KPV/MMT/CS multifunctional medicinal nanoparticles loaded with cyclosporine A (CyA). In this study, KPV is utilized as a ligand for PepT1 to achieve targeting delivery.…”

Section: Oral Delivery Of Biologics In Ibd Treatmentmentioning

confidence: 99%

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Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

Zhang

Michalowski

Beloqui

2021

Front. Bioeng. Biotechnol.

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Inflammatory bowel disease (IBD) has been posed as a great worldwide health threat. Having an onset during early adulthood, IBD is a chronic inflammatory disease characterized by remission and relapse. Due to its enigmatic etiology, no cure has been developed at the moment. Conventionally, steroids, 5-aminosalicylic acid, and immunosuppressants have been applied clinically to relieve patients’ syndrome which, unfavorably, causes severe adverse drug reactions including diarrhea, anemia, and glaucoma. Insufficient therapeutic effects also loom, and surgical resection is mandatory in half of the patients within 10 years after diagnosis. Biologics demonstrated unique and differentiative therapeutic mechanism which can alleviate the inflammation more effectively. However, their application in IBD has been hindered considering their stability and toxicity. Scientists have brought up with the concept of nanomedicine to achieve the targeted drug delivery of biologics for IBD. Here, we provide an overview of biologics for IBD treatment and we review existing formulation strategies for different biological categories including antibodies, gene therapy, and peptides. This review highlights the current trends in oral delivery of biologics with an emphasis on the important role of nanomedicine in the development of reliable methods for biologic delivery in IBD treatment.

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Section: Therapeutic Peptidesmentioning

confidence: 99%

Section: Oral Ibd Treatment Strategiesmentioning

confidence: 99%

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Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

Zhang

Michalowski

Beloqui

2021

Front. Bioeng. Biotechnol.

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“…However, the transporter was found to be anomalously overexpressed in inflammatory colonic epithelial cells and macrophages [ 132 , 133 ], indicating that PepT1 could be a promising target for the delivery of drugs to treat colonic inflammation. Wu et al modified a PLGA nanoparticle with lysine-proline-valine (KPV) tripeptide to load cyclosporine A (CyA), and the resultant PepT1-targeted NPs were further coated with Montmorillonite (MMT) and chitosan (CS) to reduce CyA leakage in the upper gastrointestinal tract and enhance nanoparticle adhesion to the inflamed colon [ 134 ]. In vivo studies then showed that the CyA-PLGA-KPV/MMT/CS nanoparticles (PKMCN) specifically accumulated in the inflamed tissues and were retained at these sites for up to 36 h; they also exhibited significant therapeutic efficacy, evidenced by the improvements in body weight, colon length, and disease activity index.…”

Section: Transporter-targeted Ndds For Other Indicationsmentioning

confidence: 99%

Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery

Kou

Yao

Zhang

et al. 2020

Cancers

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Nano-devices are recognized as increasingly attractive to deliver therapeutics to target cells. The specificity of this approach can be improved by modifying the surface of the delivery vehicles such that they are recognized by the target cells. In the past, cell-surface receptors were exploited for this purpose, but plasma membrane transporters also hold similar potential. Selective transporters are often highly expressed in biological barriers (e.g., intestinal barrier, blood–brain barrier, and blood–retinal barrier) in a site-specific manner, and play a key role in the vectorial transfer of nutrients. Similarly, selective transporters are also overexpressed in the plasma membrane of specific cell types under pathological states to meet the biological needs demanded by such conditions. Nano-drug delivery systems could be strategically modified to make them recognizable by these transporters to enhance the transfer of drugs across the biological barriers or to selectively expose specific cell types to therapeutic drugs. Here, we provide a comprehensive review and detailed evaluation of the recent advances in the field of transporter-targeted nano-drug delivery systems. We specifically focus on areas related to intestinal absorption, transfer across blood–brain barrier, tumor-cell selective targeting, ocular drug delivery, identification of the transporters appropriate for this purpose, and details of the rationale for the approach.

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“…Some have used dipeptides (e.g., valine-glycine and tyrosine-valine) chemically linked to poly-lactic acid-poly-ethylene glycol (PLA-PEG) to deliver drugs. 46,47 The results from these studies have suggested that upregulated membrane proteins, especially transporters, are excellent anchors for IEC-targeted NP delivery.…”

Section: Deliverable Targets In Ibd and Corresponding Np Materials Inmentioning

confidence: 99%

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

Yang¹,

Merlin²

2019

IJN

117

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Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome-dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

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A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis

Abstract: A novel nano-system (PKMCN) with medical value could accumulate in the inflamed colon tissues and exhibit a strong anti-inflammatory effect.

Cited by 45 publications

References 50 publications

Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery

<p>Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives</p>

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