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Pharmaceutics
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Liposomes for Gene and Drug Delivery
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Liposomes for Gene and Drug Delivery

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 (31 July 2020) | Viewed by 28431

Special Issue Editors

Prof. Dr. Yoshiyuki Hattori

E-Mail Website
Guest Editor
Department of Pharmaceutics, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Interests: gene delivery; siRNA therapeutics; liposome; drug delivery system
Dr. Kumi Kawano

E-Mail Website
Guest Editor
Department of Pharmaceutics, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Interests: liposome; cancer therapy; anticancer drug; targeting

Special Issue Information

Dear Colleagues,

Recently, liposomes have received much attention as carriers for gene therapy and chemotherapy in pharmaceutical applications. The application of liposomes in these therapies improves the pharmacokinetics of genes and drugs compared to their free forms. In gene therapy, liposomal encapsulation or lipoplex formation can stabilize therapeutic genes (e.g., siRNAs, miRNAs, antisense oligonucleotides, and plasmid DNA) in blood circulation and deliver them efficiently to target tissues with minimal toxicity. Liposomal encapsulation of therapeutic agents (e.g., anticancer drugs) can reduce the side effects and enhance the therapeutic efficacy of chemotherapeutic drugs by modifying their pharmacokinetics and tissue distribution. These therapeutic outcomes are influenced by the physicochemical properties of liposomes such as particle size, surface charge, and release rate, and by their surface functionalization with polymers or targeting ligands. This Special Issue will publish articles on all aspects of liposomal gene and drug delivery systems including the design, development, and characterization of liposomal formulations, their pharmacokinetic properties, and their use in the treatment of acquired and inherited diseases.

Prof. Dr. Yoshiyuki Hattori
Dr. Kumi Kawano
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

  • liposome
  • gene delivery
  • gene therapy
  • drug delivery
  • drug targeting
  • nanomedicine
  • nanotechnology

Published Papers (7 papers)

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Research

10 pages, 2006 KiB  
Communication
Efficient Transfection of Large Plasmids Encoding HIV-1 into Human Cells—A High Potential Transfection System Based on a Peptide Mimicking Cationic Lipid
by Christopher Janich, Daniel Ivanusic, Julia Giselbrecht, Elena Janich, Shashank Reddy Pinnapireddy, Gerd Hause, Udo Bakowsky, Andreas Langner and Christian Wölk
Pharmaceutics 2020, 12(9), 805; https://doi.org/10.3390/pharmaceutics12090805 - 25 Aug 2020
Cited by 2 | Viewed by 2811
Abstract
One major disadvantage of nucleic acid delivery systems is the low transfection or transduction efficiency of large-sized plasmids into cells. In this communication, we demonstrate the efficient transfection of a 15.5 kb green fluorescent protein (GFP)-fused HIV-1 molecular clone with a nucleic acid [...] Read more.
One major disadvantage of nucleic acid delivery systems is the low transfection or transduction efficiency of large-sized plasmids into cells. In this communication, we demonstrate the efficient transfection of a 15.5 kb green fluorescent protein (GFP)-fused HIV-1 molecular clone with a nucleic acid delivery system prepared from the highly potent peptide-mimicking cationic lipid OH4 in a mixture with the phospholipid DOPE (co-lipid). For the transfection, liposomes were loaded using a large-sized plasmid (15.5 kb), which encodes a replication-competent HIV type 1 molecular clone that carries a Gag-internal green fluorescent protein (HIV-1 JR-FL Gag-iGFP). The particle size and charge of the generated nanocarriers with 15.5 kb were compared to those of a standardized 4.7 kb plasmid formulation. Stable, small-sized lipoplexes could be generated independently of the length of the used DNA. The transfer of fluorescently labeled pDNA-HIV1-Gag-iGFP in HEK293T cells was monitored using confocal laser scanning microscopy (cLSM). After efficient plasmid delivery, virus particles were detectable as budding structures on the plasma membrane. Moreover, we observed a randomized distribution of fluorescently labeled lipids over the plasma membrane. Obviously, a significant exchange of lipids between the drug delivery system and the cellular membranes occurs, which hints toward a fusion process. The mechanism of membrane fusion for the internalization of lipid-based drug delivery systems into cells is still a frequently discussed topic. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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12 pages, 1828 KiB  
Article
Cyclopropenium Nanoparticles and Gene Transfection in Cells
by Noam Y. Steinman, Luis M. Campos, Yakai Feng, Abraham J. Domb and Hossein Hosseinkhani
Pharmaceutics 2020, 12(8), 768; https://doi.org/10.3390/pharmaceutics12080768 - 13 Aug 2020
Cited by 14 | Viewed by 3555
Abstract
Non-viral vectors for the transfection of genetic material are at the frontier of medical science. In this article, we introduce for the first time, cyclopropenium-containing nanoparticles as a cationic carrier for gene transfection, as an alternative to the common quaternary ammonium transfection agents. [...] Read more.
Non-viral vectors for the transfection of genetic material are at the frontier of medical science. In this article, we introduce for the first time, cyclopropenium-containing nanoparticles as a cationic carrier for gene transfection, as an alternative to the common quaternary ammonium transfection agents. Cyclopropenium-based cationic nanoparticles were prepared by crosslinking poly(ethylene imine) (PEI) with tetrachlorocyclopropene. These nanoparticles were electrostatically complexed with plasmid DNA into nanoparticles (~50 nm). Their cellular uptake into F929 mouse fibroblast cells, and their eventual expression in vitro have been described. Transfection is enhanced relative to PEI with minimal toxicity. These cyclopropenium nanoparticles possess efficient gene transfection capabilities with minimal cytotoxicity, which makes them novel and promising candidates for gene therapy. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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14 pages, 3370 KiB  
Article
Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery
by Eiji Yuba, Yoshiki Fukaya, Shin Yanagihara, Nozomi Kasho and Atsushi Harada
Pharmaceutics 2020, 12(8), 754; https://doi.org/10.3390/pharmaceutics12080754 - 11 Aug 2020
Cited by 13 | Viewed by 3938
Abstract
Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified [...] Read more.
Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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13 pages, 3060 KiB  
Article
A Novel Treatment Modality for Malignant Peripheral Nerve Sheath Tumor Using a Dual-Effect Liposome to Combine Photodynamic Therapy and Chemotherapy
by Chin-Tin Chen, Po-Chun Peng, Tsuimin Tsai, Hsiung-Fei Chien and Ming-Jen Lee
Pharmaceutics 2020, 12(4), 317; https://doi.org/10.3390/pharmaceutics12040317 - 2 Apr 2020
Cited by 12 | Viewed by 2601
Abstract
Neurofibromatosis type 1 (NF1) is an inherited neurological disorder. Approximately 5–13% of NF1 patients may develop a malignant peripheral nerve sheath tumor (MPNST), which is a neurofibrosarcoma transformed from the plexiform neurofibroma or schwannoma. Given the large size and easy metastasis of MPNST, [...] Read more.
Neurofibromatosis type 1 (NF1) is an inherited neurological disorder. Approximately 5–13% of NF1 patients may develop a malignant peripheral nerve sheath tumor (MPNST), which is a neurofibrosarcoma transformed from the plexiform neurofibroma or schwannoma. Given the large size and easy metastasis of MPNST, it remains difficult to be cured by either surgical or conventional chemotherapy. In this study, we investigated the possibility of combining photodynamic therapy (PDT) and chemotherapy to treat MPNST by using a dual-effect liposome (named as PL-cDDP-Ce6), in which a chemotherapeutic agent, cisplatin (cDDP), and photosensitizer, chlorine e6 (Ce6) were encapsulated in the same carrier. The cytotoxic effect of PL-cDDP-Ce6 against MPNST cells was significantly higher than cells treated with liposomal cDDP or Ce6 alone or in combination after light irradiation. Treatment with the dual-effect liposomes in mice bearing xenograft MPNST tumor reveals a significant increase in survival rate compared to those treated with liposomal cDDP and Ce6 in combination. Moreover, there is no weight loss or derangements of serum biochemistry. In conclusion, this study demonstrates the clinical potential and advantage of using this liposomal drug for the treatment of MPNST. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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17 pages, 3481 KiB  
Article
Spironolactone-Loaded LeciPlexes as Potential Topical Delivery Systems for Female Acne: In Vitro Appraisal and Ex Vivo Skin Permeability Studies
by Ayman Salama, Mohamed Badran, Mohammed Elmowafy and Ghareb M. Soliman
Pharmaceutics 2020, 12(1), 25; https://doi.org/10.3390/pharmaceutics12010025 - 25 Dec 2019
Cited by 37 | Viewed by 4761
Abstract
Spironolactone (SP), an aldosterone antagonist with anti-androgen properties, has shown promising results in the treatment of female acne. However, its systemic side effects limit its clinical benefits. This study aimed to prepare and evaluate LeciPlexes for SP topical delivery. LeciPlexes were prepared by [...] Read more.
Spironolactone (SP), an aldosterone antagonist with anti-androgen properties, has shown promising results in the treatment of female acne. However, its systemic side effects limit its clinical benefits. This study aimed to prepare and evaluate LeciPlexes for SP topical delivery. LeciPlexes were prepared by a one-step procedure and characterized using various techniques. Optimum LeciPlex preparation was incorporated into 1% methylcellulose gel and SP permeability was tested ex vivo in Sprague-Dawley rat skin. The maximum drug encapsulation efficiency obtained was 93.6 ± 6.9% and was dependent on the drug/phospholipid and surfactant/phospholipid ratios. A zeta potential of +49.3 ± 3.5 to +57.7 ± 3.3 mV and a size of 108 ± 25.3 to 668.5 ± 120.3 nm were observed for the LeciPlexes. FT-IR and DSC studies confirmed the incorporation of SP into the LeciPlexes through hydrophobic and hydrogen bonding interactions. SP release from the LeciPlex formulations was significantly slower than from the drug suspension. Cumulative SP permeated through rat skin from LeciPlex gel was about 2-fold higher than SP control gel. Cumulative SP deposited in the stratum corneum and other skin layers from the LeciPlex gel was about 1.8- and 2.6-fold higher than SP control gel, respectively. This new SP LeciPlex formulation is a promising carrier for the treatment of female acne. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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16 pages, 3494 KiB  
Article
The Impact of Solvent Selection: Strategies to Guide the Manufacturing of Liposomes Using Microfluidics
by Cameron Webb, Swapnil Khadke, Signe Tandrup Schmidt, Carla B. Roces, Neil Forbes, Gillian Berrie and Yvonne Perrie
Pharmaceutics 2019, 11(12), 653; https://doi.org/10.3390/pharmaceutics11120653 - 4 Dec 2019
Cited by 44 | Viewed by 6525
Abstract
The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in [...] Read more.
The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposome attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to isopropanol) increased the liposome particle size without impacting liposome short-term stability or release characteristics. Furthermore, solvent combinations such as methanol/isopropanol mixtures can be used to modify solvent polarity and the resultant liposome particle size. However, the impact of solvent choice on the liposome product is also influenced by the liposome formulation; liposomes containing charged lipids tended to show more sensitivity to solvent selection and formulations containing increased concentrations of cholesterol or pegylated-lipids were less influenced by the choice of solvent. Indeed, incorporation of 14 wt% or more of pegylated-lipid was shown to negate the impact of solvent selection. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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17 pages, 2810 KiB  
Article
Co-Encapsulation of Chlorin e6 and Chemotherapeutic Drugs in a PEGylated Liposome Enhance the Efficacy of Tumor Treatment: Pharmacokinetics and Therapeutic Efficacy
by Po-Chun Peng, Ruey-Long Hong, Tsuimin Tsai and Chin-Tin Chen
Pharmaceutics 2019, 11(11), 617; https://doi.org/10.3390/pharmaceutics11110617 - 17 Nov 2019
Cited by 16 | Viewed by 3345
Abstract
Long-circulating PEG-modified liposome has been shown to improve pharmacokinetic properties and reduce systemic toxicity in cancer treatment. However, drug bioavailability from liposome remains a major challenge to the improvement of its therapeutic efficacy. Previously, we designed a PEGylated dual-effect liposome (named as PL-Dox-Ce6) [...] Read more.
Long-circulating PEG-modified liposome has been shown to improve pharmacokinetic properties and reduce systemic toxicity in cancer treatment. However, drug bioavailability from liposome remains a major challenge to the improvement of its therapeutic efficacy. Previously, we designed a PEGylated dual-effect liposome (named as PL-Dox-Ce6) with chlorin e6 incorporated in the lipid bilayer and Doxorubicin encapsulated in the interior. In this study, another dual-effect liposome with cisplatin encapsulated in the interior was further developed. The pharmacokinetics of these two dual-effect liposomes were studied in tumor-bearing mice. Based on the kinetic data of tumor and plasma, light irradiation was applied onto the tumors at different time points after drug administration to compare the therapeutic efficacy. We demonstrated that a single dose of the dual-effect liposomes combined with two doses of light irradiation can completely eradicate over 90% of the tumor in mice alone with significant survival rate and no toxicity. Thus, this study established a platform that utilizes the dual-effect liposome which combines photodynamic therapy and chemotherapy to improve the therapeutic outcomes of tumors. Full article
(This article belongs to the Special Issue Liposomes for Gene and Drug Delivery)
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