Special Issue "Liposome Technologies"

Guest Editor
Dr. Timothy D. Heath
School of Pharmacy University of Wisconsin 777 Highland Ave. Madison, WI 53705, USA
Website: http://apps.pharmacy.wisc.edu/sopdir/29
E-Mail: tdheath@wisc.edu
Interests: liposome technology; drug delivery and gene delivery systems; drug carrier

Dear Colleagues,

This special issue “Liposome Technologies” will deal with all aspects of liposome-mediated delivery of therapeutic agents. Therapeutic agents may include drugs, or any biological agents including DNA, RNA, proteins, or antigens for vaccination. The mode of delivery may be passive or ligand-mediated targeting, controlled release, or systemic localization. The topic of papers can be the preparation of novel formulations, study of their properties, the in vivo or in vitro testing of such agents for their efficacy or stability, or study of their localization within cells in vitro or in vivo. In addition to papers that focus directly on therapeutic applications, studies dealing with the fundamental aspects of liposomes of concern for their use in drug delivery will also be considered.

Dr. Timothy D. Heath
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 quarterly 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 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• liposome
• drug delivery
• cationic lipids
• gene delivery
• controlled release
• liposome targeting
• liposome-mediated therapeutics
• membrane permeability
• liposome-based vaccines

Type of Paper: Review
Title: Advances in Lipid Nanoparticles for siRNA Delivery
Authors: Yuen Yi C. Tam and Pieter R. Cullis
Affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
Abstract: Technological advances in both siRNA (small interfering RNA) and whole genome sequencing have offered great potential to translate genetic information into siRNA-based drugs to halt the synthesis of most disease-causing proteins. Despite the powerful promises as a drug, siRNA requires sophisticated delivery vehicle because of its rapid degradation in the circulation, inefficient accumulation in target tissues and inability to cross cell membranes to access the cytoplasm where it functions. Lipid nanoparticles are the leading delivery technology for siRNA with 6 products in clinical trials. Here, we focus on the recent developments of lipid nanoparticles for potent gene silencing using siRNA.

Title: Cationic Liposomes as Adjuvant for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Bilayer Composition and Immune Modulators
Authors: Christophe Barnier Quer, Abdelrahman Elsharkawy, Hizel Ashti, Stefan Romeijn, Alexander Kros and Wim Jiskoot
Abstract: The influence of cationic liposome composition, antigen (influenza hemagglutinin [HA]) loading method and coencapsulation of immune modulators on the immunogenicity of the antigen was studied. Liposomes consisting of DPPC or cholesterol and a cationic compound (DC-Chol, DDA or eDPPC) with or without immune modulator (CpG, imiquimod, TDB or DDA-mannose) were produced. Mice were immunized with the formulations and sera were analyzed for IgG subclass and hemagglutation inhibition titers. Results showed that (1) liposome-adsorbed HA is more immunogenic than encapsulated HA, (2) eDPPC:Chol liposomes are a stronger adjuvant than eDPPC:DPPC liposomes, and (3) CpG and DDA-mannose enhance the adjuvant effect of cationic liposomes.

Title: Inhalable Phospholipid and Lipopolymeric Self-Assemblies for Targeted Pulmonary Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers
Authors: Heidi M. Mansour^1,* and Don Hayes, Jr.^2,3
Affiliations: ¹The University of Arizona-Tucson, College of Pharmacy, Tucson, AZ, USA
² The Ohio State University College of Medicine, Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Columbus, OH, USA
³ The Ohio State University College of Medicine, The Davis Heart and Lung Research Institute, Columbus, OH, USA
*Correspondence: Heidi M. Mansour, Ph.D., E-mail: mansour@pharmacy.arizona.edu.
Abstract: Inhalation aerosols have been and continue to be used in the successful targeted treatment and prevention of various pulmonary diseases.  Inhaled aerosols of liposomal self-assemblies for drug, gene, and vaccine delivery have been demonstrated in the targeted treatment and prevention of pulmonary disease as inhaled colloidal dispersion aerosols.  The design and development of solid-state controlled release respirable microparticles and nanoparticles of phospholipid and PEGylated phospholipid self-assemblies for dry powder inhalation aerosol delivery can offer many unique advantages. This paper will describe the fundamental aspects and cutting-edge research in aerosolized phospholipids and lipopolymeric self-assemblies as dry powder inhalers (DPIs) for the treatment and prevention of lung disease.
Keywords: respiratory aerosols; pulmonary nanomedicine; drug, gene, and vaccine delivery; lung; controlled release modeling; solid-state; particle engineering design; molecular pharmaceutics; powder technology; in Vitro; in Vivo

Title: Serum and CSF Cytokine Responses after a Single Lipoplex Infusion into the Cisterna Magna of Rhesus Macaques: A Comparison and Review of Immune Responses after Delivery of Non-Viral and Viral Vectors
Authors: Srikanth Yellayi, Brendan A. Hilliard, Reed F. Johnson, Alice Tarantal and J.G. Hecker
Affiliation: University of Pennsylvania, Harborview Medical Center, Box, Seattle, WA 98104, USA
Abstract: Immune and inflammatory responses to exogenous therapeutics, including small molecules, proteins, and nucleic acids, limit widespread clinical applications of these therapeutics. Immune reactions to non-immune-stimulatory therapies (i.e. not vaccines) can limit viral and non viral delivery, impair efficacy, eliminate redosing, and cause severe systemic immune reactions. Previous reports have characterized immune and inflammatory responses after viral vectors, in particular Adeno and Adeno-associated vectors, but similar descriptions of immune responses after non-viral vectors have been lacking. We previously showed that a vector:lipid system comprised of plasmid DNA or mRNA and cationic lipid (lipoplex), when injected into the cerebral spinal fluid (CSF) of the rat can efficiently deliver reporter genes that lead to widespread reporter protein expression in the Central Nervous System (CNS). It is critical for further development of CNS gene delivery to fully understand the antigenic properties of the delivery vector and of the expression produce. To further characterize non-viral CNS nucleic acids delivery we measured the in vivo time course of multiple markers of inflammatory and immune response after a single intrathecal injection into the CSF in the rhesus macaque. We infused a formulated lipoplex containing the plasmid DNA encoding for GFP and the cationic lipid MLRI into the cisterna magna. We followed cytokines and immune responses over time by analysis of CSF and plasma samples that were collected at serial time points after intrathecal injection.  Our results show that non-viral lipoplexes produce only a small and brief immune or inflammatory response in the CNS of non-human primates at times from 24 hours to 6 months after injection and no detectable serum response in the blood. Finally, we confirm the distribution of eGFP in brain by immunohistochemical staining from an animal euthanized 24 hours after injection at the peak of reporter enzyme expression.
Keywords: immune; inflammatory response; CNS; brain; non-viral; gene therapy; siRNA; lipoplex; cytokines; multiplex

Title: Model-Based Development of Liposomal Formulations in Oncology
Authors: Sihem Ait-Oudhia, Donald E. Mager and Robert M. Straubinger
Abstract: Liposomal formulations of anticancer agents have been developed to enhance the therapeutic efficacy and/or reducing toxicities via several mechanisms. Despite the clinical introduction and approval of efficacious liposome-based chemotherapeutics, considerable developmental challenges remain, including optimizing biodistribution, the release rates of encapsulated drug, and uptake by target cells. Mathematical modeling has become an essential tool for understanding and predicting drug transport, uptake, and disposition processes and their role in liposome-based antitumor therapy outcomes. Here we review and evaluate relevant pharmacokinetic/pharmacodynamic models describing the behavior of liposomal formulations in oncology that incorporate key physical, biochemical, and physiological processes involved in drug delivery, cellular uptake, and antitumor response.

Type of Paper: Review
Title: Bioavailability of Polyphenol Liposomes: A Challenge Ahead
Authors: Nathalie Mignet, Johanne Seguin, Yasmine S. Touil and Guy G. Chabot
Abstract: Dietary polyphenols, including flavonoids, have long been recognized as a source of important molecules involved in the prevention of several diseases including cancer. However, because of their poor bioavailability, polyphenols remain difficult to be employed clinically. Over the past years a renewed interest has been devoted to the use of liposomes as carriers aimed at increasing the bioavailability and hence the therapeutic benefits of polyphenols. In this paper, we review the causes linked to the poor bioavailability of polyphenols and concentrate on their liposomal formulations which offer a means of improving their pharmacokinetics and pharmacodynamics. The problems linked to their development and their potential therapeutic advantages are reviewed. Future directions for liposomal polyphenol development will finally be suggested.