Drug Delivery Systems for Oral Immunotherapy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 16797

Special Issue Editor


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Guest Editor
Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea
Interests: drug delivery system; nanomedicine; molecular imaging; immunotherapy; gut microbiome; apoptosis

Special Issue Information

Dear Colleagues,

Various gastrointestinal factors (GIT factors) including mucosal immune systems, the intestinal barrier, and gut microbiota are highly associated with the induction, development, severity, and treatment of local GIT diseases such as inflammatory bowel disease (IBD) as well as various systemic diseases such as cancer, metabolic diseases, hyperglycemia, and CNS diseases. The selective delivery of drugs including antigens, immunomodulators, intestinal-barrier-function enhancers, and gut-microbiome manipulators to address one or a combination of the GIT factors has shown promising results for oral vaccines, oral tolerance, GIT disease (e.g., IBD) treatment, and the management of various systemic diseases (e.g., cancer). However, physiochemical and biological barriers in the GIT tract should be overcome to achieve each goal. Thus, numerous drug-delivery systems including microparticles, nanomedicines, and other drug-delivery formulations have emerged as attractive options for not only overcoming barriers but also selectively delivering loaded cargo to GIT target sites.

This Special Issue will cover a wide range of current topics related to GIT factors, targeting delivery strategies for oral vaccines, oral tolerance, IBD treatment, and other systemic diseases.

Dr. Yonghyun Lee
Guest Editor

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Keywords

  • oral drug delivery
  • nanomedicine
  • mucosal immunology
  • oral vaccine
  • oral tolerance
  • intestinal barrier
  • gut microbiome
  • inflammatory bowel diseases
  • cancer

Published Papers (6 papers)

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Research

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19 pages, 1927 KiB  
Article
Towards Development of a Non-Toxigenic Clostridioides difficile Oral Spore Vaccine against Toxigenic C. difficile
by Jaime Hughes, Carl Aston, Michelle L. Kelly and Ruth Griffin
Pharmaceutics 2022, 14(5), 1086; https://doi.org/10.3390/pharmaceutics14051086 - 19 May 2022
Cited by 7 | Viewed by 2314
Abstract
Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local [...] Read more.
Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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14 pages, 2548 KiB  
Article
Oral Immunogenicity of Enterotoxigenic Escherichia coli Outer Membrane Vesicles Encapsulated into Zein Nanoparticles Coated with a Gantrez® AN–Mannosamine Polymer Conjugate
by Melibea Berzosa, Alzbeta Nemeskalova, Alba Calvo, Gemma Quincoces, María Collantes, Felix Pareja, Carlos Gamazo and Juan Manuel Irache
Pharmaceutics 2022, 14(1), 123; https://doi.org/10.3390/pharmaceutics14010123 - 4 Jan 2022
Cited by 4 | Viewed by 1952
Abstract
Enterotoxigenic Escherichia coli (ETEC) represents a major cause of morbidity and mortality in the human population. In particular, ETEC infections affect children under the age of five from low-middle income countries. However, there is no licensed vaccine against this pathogen. ETEC vaccine development [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) represents a major cause of morbidity and mortality in the human population. In particular, ETEC infections affect children under the age of five from low-middle income countries. However, there is no licensed vaccine against this pathogen. ETEC vaccine development is challenging since this pathotype expresses a wide variety of antigenically diverse virulence factors whose genes can be modified due to ETEC genetic plasticity. To overcome this challenge, we propose the use of outer membrane vesicles (OMVs) isolated from two ETEC clinical strains. In these OMVs, proteomic studies revealed the presence of important immunogens, such as heat-labile toxin, colonization factors, adhesins and mucinases. Furthermore, these vesicles proved to be immunogenic after subcutaneous administration in BALB/c mice. Since ETEC is an enteropathogen, it is necessary to induce both systemic and mucosal immunity. For this purpose, the vesicles, free or encapsulated in zein nanoparticles coated with a Gantrez®–mannosamine conjugate, were administered orally. Biodistribution studies showed that the encapsulation of OMVs delayed the transit through the gut. These results were confirmed by in vivo study, in which OMV encapsulation resulted in higher levels of specific antibodies IgG2a. Further studies are needed to evaluate the protection efficacy of this vaccine approach. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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15 pages, 2010 KiB  
Article
Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents
by Jaeok Lee, Jiyeon Kang, Na-Yun Kwon, Aneesh Sivaraman, Ravi Naik, So-Young Jin, A. Reum Oh, Jae-Ho Shin, Younghwa Na, Kyeong Lee and Hwa-Jeong Lee
Pharmaceutics 2021, 13(4), 559; https://doi.org/10.3390/pharmaceutics13040559 - 15 Apr 2021
Cited by 17 | Viewed by 2468
Abstract
P-glycoprotein (P-gp) inhibition has been studied to overcome multidrug resistance in cancer chemotherapy but failed in clinical trials due to low/toxic effects. Recently, a dual modulation of transporters and natural derivatives have been examined to surmount this limitation. We examined breast cancer resistance [...] Read more.
P-glycoprotein (P-gp) inhibition has been studied to overcome multidrug resistance in cancer chemotherapy but failed in clinical trials due to low/toxic effects. Recently, a dual modulation of transporters and natural derivatives have been examined to surmount this limitation. We examined breast cancer resistance protein (BCRP) inhibition in vitro and in vivo by P-gp inhibitors derived from natural compounds in previous studies. P-gp inhibitors increased the accumulation of the anticancer drug, topotecan (TPT)—a substrate of P-gp and BCRP, albeit with higher affinity for BCRP—in BCRP-overexpressing cells, resulting in cell death. These dual inhibitors, when orally co-administered with TPT, enhanced TPT bioavailability with slightly reduced total oral clearance (Clt/F) in rats. In xenograft mice, they strengthened oral TPT-induced tumor reduction with no alterations in body weight. Moreover, we investigated the effects of an oral drug formulation (Cremophor® EL, Tween® 80, and polyethylene glycol 400) on the transporters function. The excipients increased TPT accumulation in P-gp- or BCRP-overexpressing cells. Oral TPT bioavailability was higher with the formulation than with a control, as shown by the increases in the maximum plasma concentration (Cmax) and the area under the plasma concentration–time curve from zero to infinity (AUCINF) (p< 0.01). Therefore, oral TPT bioavailability was enhanced by P-gp/BCRP dual inhibition, which resulted in a formulation-mediated increase in absorption and decrease in elimination, and a dual inhibitor-mediated decrease in elimination. These results suggest that the combination of dual inhibition by a natural derivative and the drug formulation can be a useful clinical approach. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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Review

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21 pages, 3603 KiB  
Review
Oral Nanomedicines for siRNA Delivery to Treat Inflammatory Bowel Disease
by Jongyoon Shinn, Juyeon Lee, Seon Ah Lee, Seon Ju Lee, Ah Hyun Choi, Jung Seo Kim, Su Jin Kim, Hyo Jin Kim, Cherin Lee, Yejin Kim, Joohyeon Kim, Jonghee Choi, Byungchae Jung, Taeho Kim, HyeonTaek Nam, Hyungjun Kim and Yonghyun Lee
Pharmaceutics 2022, 14(9), 1969; https://doi.org/10.3390/pharmaceutics14091969 - 19 Sep 2022
Cited by 7 | Viewed by 2673
Abstract
RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both [...] Read more.
RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both the delivery of siRNA to the target site and the action of siRNA drugs at the target site. In this review, we first discuss various physicochemical and biological barriers in the GI tract. Furthermore, we present recent strategies and the progress of oral siRNA delivery strategies to treat IBD. Finally, we consider the challenges faced in the use of these strategies and future directions of oral siRNA delivery strategies. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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20 pages, 3077 KiB  
Review
Targeting the Gut Mucosal Immune System Using Nanomaterials
by Jacob McCright, Ann Ramirez, Mayowa Amosu, Arnav Sinha, Amanda Bogseth and Katharina Maisel
Pharmaceutics 2021, 13(11), 1755; https://doi.org/10.3390/pharmaceutics13111755 - 21 Oct 2021
Cited by 9 | Viewed by 3935
Abstract
The gastrointestinal (GI) tract is one the biggest mucosal surface in the body and one of the primary targets for the delivery of therapeutics, including immunotherapies. GI diseases, including, e.g., inflammatory bowel disease and intestinal infections such as cholera, pose a significant public [...] Read more.
The gastrointestinal (GI) tract is one the biggest mucosal surface in the body and one of the primary targets for the delivery of therapeutics, including immunotherapies. GI diseases, including, e.g., inflammatory bowel disease and intestinal infections such as cholera, pose a significant public health burden and are on the rise. Many of these diseases involve inflammatory processes that can be targeted by immune modulatory therapeutics. However, nonspecific targeting of inflammation systemically can lead to significant side effects. This can be avoided by locally targeting therapeutics to the GI tract and its mucosal immune system. In this review, we discuss nanomaterial-based strategies targeting the GI mucosal immune system, including gut-associated lymphoid tissues, tissue resident immune cells, as well as GI lymph nodes, to modulate GI inflammation and disease outcomes, as well as take advantage of some of the primary mechanisms of GI immunity such as oral tolerance. Full article
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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20 pages, 1773 KiB  
Review
Immune Checkpoint and Anti-Angiogenic Antibodies for the Treatment of Non-Small Cell Lung Cancer in the European Union and United States
by Marion Ferreira, Thomas Secher, Nathalie Heuze-Vourc’H and Karen L Reckamp
Pharmaceutics 2021, 13(6), 912; https://doi.org/10.3390/pharmaceutics13060912 - 21 Jun 2021
Cited by 2 | Viewed by 2539
Abstract
Several types of antibodies (Abs) are currently used in non-small cell lung cancer (NSCLC). Anti-angiogenic and immune checkpoint inhibitor (ICI) Abs are the most frequent treatments used alone or with chemotherapy in metastatic NSCLC, for the front line and beyond. Considering the many [...] Read more.
Several types of antibodies (Abs) are currently used in non-small cell lung cancer (NSCLC). Anti-angiogenic and immune checkpoint inhibitor (ICI) Abs are the most frequent treatments used alone or with chemotherapy in metastatic NSCLC, for the front line and beyond. Considering the many therapeutic options for locally advanced and metastatic lung cancer and differences in use according to geographic area, we present here a comprehensive review of the marketed ICI and anti-angiogenic Abs approved in the European Union (EU) and the US to treat locally advanced and metastatic NSCLC patients. We briefly describe the different molecules and their development in thoracic oncology and compare pharmacokinetic data, processing decision algorithms and marketing authorizations by the EMA and US Food and Drug Administration (FDA). Full article
(This article belongs to the Special Issue Drug Delivery Systems for Oral Immunotherapy)
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