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Pharmaceutics
Special Issues
Nanoparticle-Based Drug Delivery Systems for Immunomodulation
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Nanoparticle-Based Drug Delivery Systems for Immunomodulation

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 25161

Special Issue Editors

Prof. Dr. Alf Lamprecht

E-Mail Website
Guest Editor
1. Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany
2. PEPITE EA4267, University of Burgundy/Franche-Comté, 25000 Besançon, France
Interests: nanoparticle-based delivery across/towards inflamed barriers; drying techniques for micro/nanoparticle formulation
Dr. Maryam A. Shetab Boushehri

E-Mail Website
Guest Editor
Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany
Interests: nanoparticle-mediated cancer immunotherapy and vaccination

Special Issue Information

Dear Colleagues,

The proposed Special Issue seeks to elaborate on the immunological properties of nanomaterials, both in the presence and absence of immunomodulating cargos. Within the context of the former, the potentials of nanocarriers for targeted drug delivery in autoimmune and immune-mediated disorders, along with their ability to target various components of the immune system for immunotherapeutic purposes and the treatment of immune-related viral diseases (e.g. AIDS) will be debated. In the case of the latter, a discussion of the nanoparticle interaction with the immune system in the absence of any drug load, and the potential hazards and therapeutic benefits associated therewith will be presented. This Special Issue will provide a comprehensive overview of nanoparticles’ ability to modulate the immune response, and their potentials to target the immune-related conditions for drug delivery. It will explore the potential immunotoxicological hazards of such interactions, and debate how these can be exploited for therapeutic purposes.

Prof. Dr. Alf Lamprecht
Dr. Maryam A. Shetab Boushehri
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nanoparticles
  • Immune modulation
  • Targeted delivery
  • Immune-mediated disorders
  • Autoimmune disorders
  • Immunotherapy and vaccination
  • Immune-related viral diseases
  • Immune activation
  • Immune inhibition

Published Papers (7 papers)

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Research

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13 pages, 1366 KiB  
Article
Adjuvant Antitumor Immunity Contributes to the Overall Antitumor Effect of Pegylated Liposomal Doxorubicin (Doxil®) in C26 Tumor-Bearing Immunocompetent Mice
by Takuma Takayama, Taro Shimizu, Amr S. Abu Lila, Yuki Kanazawa, Hidenori Ando, Yu Ishima and Tatsuhiro Ishida
Pharmaceutics 2020, 12(10), 990; https://doi.org/10.3390/pharmaceutics12100990 - 19 Oct 2020
Cited by 6 | Viewed by 2579
Abstract
Doxorubicin (DXR) has been reported to have direct cytotoxicity against cancer cells and indirect immunotoxicity by modulation of host antitumor immunity. Hence, it may prevent cancer progression by a dual mechanism. Doxil®, a formulation of DXR encapsulated in polyethylene glycol modified [...] Read more.
Doxorubicin (DXR) has been reported to have direct cytotoxicity against cancer cells and indirect immunotoxicity by modulation of host antitumor immunity. Hence, it may prevent cancer progression by a dual mechanism. Doxil®, a formulation of DXR encapsulated in polyethylene glycol modified (PEGylated) liposomes, is the most widely used of the clinically approved liposomal anticancer drugs. However, the effect of Doxil® on host antitumor immunity is not well understood. In this study, Doxil® efficiently suppressed tumor growth in immunocompetent mice bearing C26 murine colorectal carcinomas, but not in T cell-deficient nude mice, indicating a contribution of T cells to the overall antitumor effect of Doxil®. In immunocompetent mice, Doxil® increased major histocompatibility complex (MHC-1) levels in C26 tumors, which may be an indicator of increased immunogenicity of tumor cells, and potentially amplified tumor immunogenicity by decreasing immunosuppressive cells such as regulatory T cells, tumor-associated microphages and myeloid-derived suppressor cells that collectively suppress T cell-mediated antitumor responses. This suggests that encapsulation of DXR into PEGylated liposomes increased the therapeutic efficacy of DXR though effects on host antitumor immunogenicity in addition to direct cytotoxic effects on tumor cells. This report describes the role of host antitumor immunity in the overall therapeutic effects of Doxil®. Manipulating pharmacokinetics and biodistribution of chemotherapeutic agents with immunomodulatory properties may increase their therapeutic efficacies by amplifying host antitumor immunity in addition to direct cytotoxic effects on tumor cells. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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15 pages, 4061 KiB  
Article
Mesenchymal Stem Cell Derived Biocompatible Membrane Vesicles Demonstrate Immunomodulatory Activity Inhibiting Activation and Proliferation of Human Mononuclear Cells
by Marina O. Gomzikova, Sevindzh K. Kletukhina, Sirina V. Kurbangaleeva, Olga A. Neustroeva, Olga S. Vasileva, Ekaterina E. Garanina, Svetlana F. Khaiboullina and Albert A. Rizvanov
Pharmaceutics 2020, 12(6), 577; https://doi.org/10.3390/pharmaceutics12060577 - 23 Jun 2020
Cited by 15 | Viewed by 2717
Abstract
Immune-mediated diseases are characterized by abnormal activity of the immune system. The cytochalasin B-induced membrane vesicles (CIMVs) are innovative therapeutic instruments. However, the immunomodulating activity of human mesenchymal stem cell (MSC)-derived CIMVs (CIMVs-MSCs) remains unknown. Therefore, we sought to investigate the immunological properties [...] Read more.
Immune-mediated diseases are characterized by abnormal activity of the immune system. The cytochalasin B-induced membrane vesicles (CIMVs) are innovative therapeutic instruments. However, the immunomodulating activity of human mesenchymal stem cell (MSC)-derived CIMVs (CIMVs-MSCs) remains unknown. Therefore, we sought to investigate the immunological properties of CIMVs-MSCs and evaluate their effect on human peripheral blood mononuclear cells (PBMCs). We found that CIMVs-MSCs are primarily uptaken by monocytes and B-cells. Additionally, we demonstrated that CIMVs-MSCs inhibit phytohemagglutinin (PHA)-induced proliferation of PBMCs, with more pronounced effect on T-lymphocytes expansion as compared to that of B-cells. In addition, activation of T-helpers (CD4+CD25+), B-cells (CD19+CD25+), and T-cytotoxic lymphocytes (CD8+CD25+) was also significantly suppressed by CIMVs-MSCs. Additionally, CIMVs-MSCs decreased secretion of epidermal growth factor (EGF) and pro-inflammatory Fractalkine in a population of PBMCs, while the releases of FGF-2, G-CSF, anti-inflammatory GM-CSF, MCP-3, anti-inflammatory MDC, anti-inflammatory IL-12p70, pro-inflammatory IL-1b, and MCP-1 were increased. We analyzed the effect of CIMVs-MSCs on an isolated population of CD4+ and CD8+ T-lymphocytes and demonstrated their different immune response and cytokine secretion. Finally, we observed that no xenogeneic nor allogeneic transplantation of CIMVs induced an immune response in mice. Our data suggest that CIMVs-MSCs have immunosuppressive properties, are potential agents for immunomodulating treatment, and are worthy of further investigation. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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12 pages, 2135 KiB  
Article
A Solid-in-Oil Nanodispersion System for Transcutaneous Immunotherapy of Cow’s Milk Allergies
by Momoko Kitaoka, Wei Xiao, Qingliang Kong, Yoshiro Tahara, Noriho Kamiya and Masahiro Goto
Pharmaceutics 2020, 12(3), 205; https://doi.org/10.3390/pharmaceutics12030205 - 27 Feb 2020
Cited by 4 | Viewed by 2885
Abstract
An allergy to cow’s milk proteins is the most common food allergy in infants and toddlers. Conventional oral immunotherapy for cow’s milk allergies requires hospital admission due to the risk of severe allergic reactions, including anaphylaxis. Therefore, a simpler and safer immunotherapeutic method [...] Read more.
An allergy to cow’s milk proteins is the most common food allergy in infants and toddlers. Conventional oral immunotherapy for cow’s milk allergies requires hospital admission due to the risk of severe allergic reactions, including anaphylaxis. Therefore, a simpler and safer immunotherapeutic method is desirable. We examined transcutaneous immunotherapy with a solid-in-oil (S/O) system. In the S/O system, nano-sized particles of proteins are dispersed in an oil-vehicle with the assistance of nonionic surfactants. In the present study, the S/O system enhanced the skin permeation of the allergen molecule β-lactoglobulin (BLG), as compared with a control PBS solution. The patches containing BLG in the S/O nanodispersion skewed the immune response in the allergy model mice toward T helper type 1 immunity, indicating the amelioration of allergic symptoms. This effect was more pronounced when the immunomodulator resiquimod (R-848) was included in the S/O system. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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14 pages, 2631 KiB  
Article
Transcutaneous Delivery of Immunomodulating Pollen Extract-Galactomannan Conjugate by Solid-in-Oil Nanodispersions for Pollinosis Immunotherapy
by Qingliang Kong, Kouki Higasijima, Rie Wakabayashi, Yoshiro Tahara, Momoko Kitaoka, Hiroki Obayashi, Yanting Hou, Noriho Kamiya and Masahiro Goto
Pharmaceutics 2019, 11(11), 563; https://doi.org/10.3390/pharmaceutics11110563 - 30 Oct 2019
Cited by 6 | Viewed by 2925
Abstract
Japanese cedar pollinosis is a type I allergic disease and has already become a major public health problem in Japan. Conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) cannot meet patients’ needs owing to the side effects caused by both the use of [...] Read more.
Japanese cedar pollinosis is a type I allergic disease and has already become a major public health problem in Japan. Conventional subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) cannot meet patients’ needs owing to the side effects caused by both the use of conventional whole antigen molecules in the pollen extract and the administration routes. To address these issues, a surface-modified antigen and transcutaneous administration route are introduced in this research. First, the pollen extract (PE) was conjugated to galactomannan (PE-GM) to mask immunoglobulin E (IgE)-binding epitopes in the PE to avoid side effects. Second, as a safer alternative to SCIT and SLIT, transcutaneous immunotherapy (TCIT) with a solid-in-oil (S/O) nanodispersion system carrying PE-GM was proposed. Hydrophilic PE-GM was efficiently delivered through mouse skin using S/O nanodispersions, reducing the antibody secretion and modifying the type 1 T helper (Th1)/ type 2 T helper (Th2) balance in the mouse model, thereby demonstrating the potential to alleviate Japanese cedar pollinosis. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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9 pages, 3002 KiB  
Communication
Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation
by Jingnan Zhao
Pharmaceutics 2019, 11(3), 143; https://doi.org/10.3390/pharmaceutics11030143 - 25 Mar 2019
Cited by 12 | Viewed by 3410
Abstract
Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 [...] Read more.
Gold nanocages (AuNCs) are biocompatible and porous nanogold particles that have been widely used in biomedical fields. In this study, hyaluronic acid (HA) and peptide- modified gold nanocages (HA-AuNCs/T/P) loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) were prepared to investigate their potential for combating inflammation. TPCA-1 was released from AuNCs, intracellularly when HA was hydrolyzed by hyaluronidase. HA-AuNCs/T/P show a much higher intracellular uptake than AuNCs/T/P, and exhibit a much higher efficacy on the suppression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) than free TPCA-1, suggesting great improvement to the anti-inflammatory efficacy of TPCA-1 through the application of AuNCs. HA-AuNCs/T/P can also reduce the production of reactive oxygen species in inflammatory cells. This study suggests that HA-AuNCs/T/P may be potential agents for anti-inflammatory treatment, and are worthy of further investigation. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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Review

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25 pages, 2454 KiB  
Review
Liposome-Based Drug Delivery Systems in Cancer Immunotherapy
by Zili Gu, Candido G. Da Silva, Koen Van der Maaden, Ferry Ossendorp and Luis J. Cruz
Pharmaceutics 2020, 12(11), 1054; https://doi.org/10.3390/pharmaceutics12111054 - 04 Nov 2020
Cited by 73 | Viewed by 7224
Abstract
Cancer immunotherapy has shown remarkable progress in recent years. Nanocarriers, such as liposomes, have favorable advantages with the potential to further improve cancer immunotherapy and even stronger immune responses by improving cell type-specific delivery and enhancing drug efficacy. Liposomes can offer solutions to [...] Read more.
Cancer immunotherapy has shown remarkable progress in recent years. Nanocarriers, such as liposomes, have favorable advantages with the potential to further improve cancer immunotherapy and even stronger immune responses by improving cell type-specific delivery and enhancing drug efficacy. Liposomes can offer solutions to common problems faced by several cancer immunotherapies, including the following: (1) Vaccination: Liposomes can improve the delivery of antigens and other stimulatory molecules to antigen-presenting cells or T cells; (2) Tumor normalization: Liposomes can deliver drugs selectively to the tumor microenvironment to overcome the immune-suppressive state; (3) Rewiring of tumor signaling: Liposomes can be used for the delivery of specific drugs to specific cell types to correct or modulate pathways to facilitate better anti-tumor immune responses; (4) Combinational therapy: Liposomes are ideal vehicles for the simultaneous delivery of drugs to be combined with other therapies, including chemotherapy, radiotherapy, and phototherapy. In this review, different liposomal systems specifically developed for immunomodulation in cancer are summarized and discussed. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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16 pages, 1935 KiB  
Review
Solid-in-Oil Nanodispersions for Transcutaneous Immunotherapy of Japanese Cedar Pollinosis
by Qingliang Kong, Momoko Kitaoka, Rie Wakabayashi, Yoshiro Tahara, Noriho Kamiya and Masahiro Goto
Pharmaceutics 2020, 12(3), 240; https://doi.org/10.3390/pharmaceutics12030240 - 07 Mar 2020
Cited by 3 | Viewed by 2672
Abstract
Japanese cedar pollinosis (JCP) is a common affliction caused by an allergic reaction to cedar pollen and is considered a disease of national importance in Japan. Antigen-specific immunotherapy (AIT) is the only available curative treatment for JCP. However, low compliance and persistence have [...] Read more.
Japanese cedar pollinosis (JCP) is a common affliction caused by an allergic reaction to cedar pollen and is considered a disease of national importance in Japan. Antigen-specific immunotherapy (AIT) is the only available curative treatment for JCP. However, low compliance and persistence have been reported among patients subcutaneously or sublingually administered AIT comprising a conventional antigen derived from a pollen extract. To address these issues, many research studies have focused on developing a safer, simpler, and more effective AIT for JCP. Here, we review the novel antigens that have been developed for JCP AIT, discuss their different administration routes, and present the effects of anti-allergy treatment. Then, we describe a new form of AIT called transcutaneous immunotherapy (TCIT) and its solid-in-oil (S/O) nanodispersion formulation, which is a promising antigen delivery system. Finally, we discuss the applications of S/O nanodispersions for JCP TCIT. In this context, we predict that TCIT delivery by using a S/O nanodispersion loaded with novel antigens may offer an easier, safer, and more effective treatment option for JCP patients. Full article
(This article belongs to the Special Issue Nanoparticle-Based Drug Delivery Systems for Immunomodulation)
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