Liposome Technologies 2015

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 April 2016) | Viewed by 77378

Special Issue Editor

Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, Universitetsveien 57, 9037 Tromsø, Norway
Interests: drug delivery; nanomedicine; liposomes; skin therapy; vaginal therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To mark 50 years of liposome research, this Special Issue on liposome technologies will include a variety of research articles, both reviews and original research contributions, dealing with liposomes. From the manufacturing methods, to the state-of-the-art research pipelines, the issue aims to provide an overview of well-established liposome technologies, marketed products, and promising new approaches in modification of liposomes for targeted drug delivery. Conventional, surface-modified, and elastic liposomes, such as deformable liposomes, ethosomes, and permeation enhancer containing vesicles, in various routes of drug administration, from topical to parenteral, will be the focus of the issue. Contributions discussing the ability of liposomes to assure prolonged, controlled and targeted drugs delivery and current limitations are invited. The industrial manufacturing aspects, as well as potential of liposomes in delivery of cosmeceuticals and nutraceuticals will also be considered.

Prof. Dr. Natasa Skalko-Basnet
Guest Editor

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Keywords

  • liposomes
  • deformable liposomes
  • transferosomes
  • ethosomes
  • formulation
  • biopharmaceuticals
  • nanotechnology

Published Papers (8 papers)

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Editorial

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1448 KiB  
Editorial
Liposomes in Drug Delivery: How It All Happened
by Gregory Gregoriadis
Pharmaceutics 2016, 8(2), 19; https://doi.org/10.3390/pharmaceutics8020019 - 24 May 2016
Cited by 53 | Viewed by 5902
Abstract
Effective delivery of drugs via liposomes in the treatment or prevention of disease is the aim of numerous researchers worldwide.[...] Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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Research

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1752 KiB  
Article
Evaluation of Extrusion Technique for Nanosizing Liposomes
by Sandy Gim Ming Ong, Mallikarjun Chitneni, Kah Seng Lee, Long Chiau Ming and Kah Hay Yuen
Pharmaceutics 2016, 8(4), 36; https://doi.org/10.3390/pharmaceutics8040036 - 21 Dec 2016
Cited by 155 | Viewed by 9700
Abstract
The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution [...] Read more.
The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution of the resultant liposomes. To compare the efficiency of different nanosizing techniques, the following techniques were used to nanosize the liposomes: extrusion, ultrasonication, freeze-thaw sonication (FTS), sonication and homogenization. The extrusion technique was found to be the most efficient, followed by FTS, ultrasonication, sonication and homogenization. The extruder used in the present study was fabricated using readily available and relatively inexpensive apparatus. Process parameters were varied in extrusion technique to study their effect on the size and size distribution of extruded liposomes. The results obtained indicated that increase in the flow rate of the extrusion process decreased the size of extruded liposomes however the size homogeneity was negatively impacted. Furthermore, the liposome size and distribution was found to decline with decreasing membrane pore size. It was found that by extruding through a filter with a pore size of 0.2 µm and above, the liposomes produced were smaller than the pore size, whereas, when they were extruded through a filter with a pore size of less than 0.2 µm the resultant liposomes were slightly bigger than the nominal pore size. Besides that, increment of extrusion temperature above transition temperature of the pro-liposome had no effect on the size and size distribution of the extruded liposomes. In conclusion, the extrusion technique was reproducible and effective among all the methods evaluated. Furthermore, processing parameters used in extrusion technique would affect the size and size distribution of liposomes. Therefore, the process parameters need to be optimized to obtain a desirable size range and homogeneity, reproducible for various in vivo applications. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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1963 KiB  
Article
Rapid Quantification and Validation of Lipid Concentrations within Liposomes
by Carla B. Roces, Elisabeth Kastner, Peter Stone, Deborah Lowry and Yvonne Perrie
Pharmaceutics 2016, 8(3), 29; https://doi.org/10.3390/pharmaceutics8030029 - 13 Sep 2016
Cited by 25 | Viewed by 8440
Abstract
Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method that allows for the [...] Read more.
Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method that allows for the rapid and simultaneous quantification of lipid concentrations within liposomal systems prepared by three liposomal manufacturing techniques (lipid film hydration, high shear mixing, and microfluidics). The ELSD system was used to quantify four lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), cholesterol, dimethyldioctadecylammonium (DDA) bromide, and ᴅ-(+)-trehalose 6,6′-dibehenate (TDB). The developed method offers rapidity, high sensitivity, direct linearity, and a good consistency on the responses (R2 > 0.993 for the four lipids tested). The corresponding limit of detection (LOD) and limit of quantification (LOQ) were 0.11 and 0.36 mg/mL (DMPC), 0.02 and 0.80 mg/mL (cholesterol), 0.06 and 0.20 mg/mL (DDA), and 0.05 and 0.16 mg/mL (TDB), respectively. HPLC-ELSD was shown to be a rapid and effective method for the quantification of lipids within liposome formulations without the need for lipid extraction processes. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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944 KiB  
Article
Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes
by Sandy Gim Ming Ong, Long Chiau Ming, Kah Seng Lee and Kah Hay Yuen
Pharmaceutics 2016, 8(3), 25; https://doi.org/10.3390/pharmaceutics8030025 - 26 Aug 2016
Cited by 146 | Viewed by 10289
Abstract
The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of [...] Read more.
The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32%) and F2(98%)], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm), MS (357 nm) and NS (813 nm)], but with essentially similar encapsulation efficiencies (about 93%). Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1) compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2), compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm) did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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Review

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794 KiB  
Review
Current Trends in Development of Liposomes for Targeting Bacterial Biofilms
by Zora Rukavina and Željka Vanić
Pharmaceutics 2016, 8(2), 18; https://doi.org/10.3390/pharmaceutics8020018 - 24 May 2016
Cited by 127 | Viewed by 10501
Abstract
Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug [...] Read more.
Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug delivery to bacterial cells and biofilms. Versatile manipulations of liposomal physicochemical properties, such as the bilayer composition, membrane fluidity, size, surface charge and coating, enable development of liposomes with desired pharmacokinetic and pharmacodynamic profiles. This review attempts to provide an unbiased overview of investigations of liposomes destined to treat bacterial biofilms. Different strategies including the recent advancements in liposomal design aiming at eradication of existing biofilms and prevention of biofilm formation, as well as respective limitations, are discussed in more details. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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2470 KiB  
Review
Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the Structure of Drug-Loaded Liposomes
by Emanuela Di Cola, Isabelle Grillo and Sandra Ristori
Pharmaceutics 2016, 8(2), 10; https://doi.org/10.3390/pharmaceutics8020010 - 28 Mar 2016
Cited by 69 | Viewed by 10076
Abstract
Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and [...] Read more.
Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and shape and (ii) cargo upload/release with unmodified properties. Structural issues are of primary importance to control the mechanism of action of loaded vectors. Overall properties, such as mean diameter and surface charge, can be obtained using bench instruments (Dynamic Light Scattering and Zeta potential). However, techniques with higher space and time resolution are needed for in-depth structural characterization. Small-angle X-ray (SAXS) and neutron (SANS) scattering techniques provide information at the nanoscale and have therefore been largely used to investigate nanovectors loaded with drugs or other biologically relevant molecules. Here we revise recent applications of these complementary scattering techniques in the field of drug delivery in pharmaceutics and medicine with a focus to liposomal carriers. In particular, we highlight those aspects that can be more commonly accessed by the interested users. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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2403 KiB  
Review
Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators
by Signe Tandrup Schmidt, Camilla Foged, Karen Smith Korsholm, Thomas Rades and Dennis Christensen
Pharmaceutics 2016, 8(1), 7; https://doi.org/10.3390/pharmaceutics8010007 - 10 Mar 2016
Cited by 145 | Viewed by 11302
Abstract
The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines [...] Read more.
The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs) concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs), which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit antigens into liposome dispersion and their optimization towards robust vaccine formulations. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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5509 KiB  
Review
Development of Liposomal Ciprofloxacin to Treat Lung Infections
by David Cipolla, Jim Blanchard and Igor Gonda
Pharmaceutics 2016, 8(1), 6; https://doi.org/10.3390/pharmaceutics8010006 - 01 Mar 2016
Cited by 144 | Viewed by 10420
Abstract
Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis [...] Read more.
Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin®) that are in development by Aradigm Corporation are described here. Full article
(This article belongs to the Special Issue Liposome Technologies 2015)
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