Next Issue
Previous Issue

Table of Contents

Pharmaceutics, Volume 5, Issue 3 (September 2013), Pages 371-507

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-10
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Involvement of Carboxylesterase in Hydrolysis of Propranolol Prodrug during Permeation across Rat Skin
Pharmaceutics 2013, 5(3), 371-384; doi:10.3390/pharmaceutics5030371
Received: 17 April 2013 / Revised: 10 June 2013 / Accepted: 18 June 2013 / Published: 1 July 2013
Cited by 6 | PDF Full-text (605 KB) | HTML Full-text | XML Full-text
Abstract
The use of a prodrug, a conjugate of an active drug with a lipophilic substituent, is a good way of increasing the cutaneous absorption of a drug. However, the activity of dermal hydrolases has rarely been investigated in humans, or experimental animals. [...] Read more.
The use of a prodrug, a conjugate of an active drug with a lipophilic substituent, is a good way of increasing the cutaneous absorption of a drug. However, the activity of dermal hydrolases has rarely been investigated in humans, or experimental animals. In the present study, we focused on the identification of rat dermal esterases and the hydrolysis of a prodrug during permeation across rat skin. We found that carboxylesterase (CES), especially the rat CES1 isozyme, Hydrolase A, is expressed in rat skin and that the hydrolysis of p-nitrophenyl acyl derivatives and caproyl-propranolol (PL) was 20-fold lower in the 9000g supernatant fraction of skin homogenate than in liver microsomes. A permeation study of caproyl-PL was performed in rat full-thickness and stripped skin using a flow-through diffusion cell. Caproyl-PL was easily partitioned into the stratum corneum and retained, not only in the stratum corneum, but also in viable epidermis and dermis. Caproyl-PL could barely be detected in the receptor fluid after application to either full-thickness or stripped skin. PL, derived from caproyl-PL, was, however, detected in receptor fluid after extensive hydrolysis of caproyl-PL in viable skin. Permeation of PL was markedly decreased under CES inhibition, indicating that the net flux of caproyl-PL is dependent on its conversion rate to PL. Full article
Open AccessArticle Transdermal Delivery of Adriamycin to Transplanted Ehrlich Ascites Tumor in Mice
Pharmaceutics 2013, 5(3), 385-391; doi:10.3390/pharmaceutics5030385
Received: 8 May 2013 / Revised: 1 July 2013 / Accepted: 3 July 2013 / Published: 11 July 2013
PDF Full-text (4025 KB) | HTML Full-text | XML Full-text
Abstract
There is considerable interest in the skin as a site of anti-cancer drug application. Nevertheless, the skin poses a formidable barrier to drug penetration, thereby limiting topical and transdermal bioavailability. However, we previously showed that a thioglycolate-based depilatory agent increases the drug [...] Read more.
There is considerable interest in the skin as a site of anti-cancer drug application. Nevertheless, the skin poses a formidable barrier to drug penetration, thereby limiting topical and transdermal bioavailability. However, we previously showed that a thioglycolate-based depilatory agent increases the drug permeability of mouse skin. In the present report, we investigated the skin permeability and efficacy of the anti-cancer drug adriamycin increased when administered transdermally to mice in combination with a thioglycolate-based depilatory agent. Adriamycin in combination with depilatory treatment reduced Ehrlich tumor growth in hairless mice about the weight and size of harvested tumors. In addition, our delivery method for adriamycin increased the therapeutic effectiveness of this agent by decreasing toxicity. Moreover, measurement of adriamycin autofluorescence revealed that topically applied adriamycin penetrate the dermis after depilatory agent treatment. These results indicate that the transdermal delivery of anti-cancer drugs is feasible by handy pretreatment of the skin with a thioglycolate-based depilatory agent. Full article
(This article belongs to the Special Issue Advanced Transdermal Drug Delivery)
Open AccessArticle Adjuvant Effect of Cationic Liposomes for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Cholesterol and Immune Modulators
Pharmaceutics 2013, 5(3), 392-410; doi:10.3390/pharmaceutics5030392
Received: 10 May 2013 / Revised: 17 July 2013 / Accepted: 17 July 2013 / Published: 25 July 2013
Cited by 8 | PDF Full-text (657 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA), DC-Chol:DPPC (1:1 molar ratio) liposomes induced the strongest immune response. However, it is not clear whether [...] Read more.
Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA), DC-Chol:DPPC (1:1 molar ratio) liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol) backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation) and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol) and a cationic compound (DC-Chol, DDA, or eDPPC) were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod). The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1) liposome-adsorbed HA is more immunogenic than encapsulated HA; (2) the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3) CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel. Full article
(This article belongs to the Special Issue Liposome Technologies)
Open AccessArticle Physical and Oxidative Stability of Uncoated and Chitosan-Coated Liposomes Containing Grape Seed Extract
Pharmaceutics 2013, 5(3), 421-433; doi:10.3390/pharmaceutics5030421
Received: 27 June 2013 / Revised: 8 August 2013 / Accepted: 12 August 2013 / Published: 20 August 2013
Cited by 11 | PDF Full-text (475 KB) | HTML Full-text | XML Full-text
Abstract
Polyphenol-rich grape seed extract (0.1 w/w%) was incorporated in liposomes (1 w/w% soy lecithin) by high pressure homogenization (22,500 psi) and coated with chitosan (0.1 w/w%). Primary liposomes and chitosan-coated secondary liposomes containing [...] Read more.
Polyphenol-rich grape seed extract (0.1 w/w%) was incorporated in liposomes (1 w/w% soy lecithin) by high pressure homogenization (22,500 psi) and coated with chitosan (0.1 w/w%). Primary liposomes and chitosan-coated secondary liposomes containing grape seed extract showed good physical stability during 98 days of storage. Most of the polyphenols were incorporated in the shell of the liposomes (85.4%), whereas only 7.6% of the polyphenols of grape seed extract were located in the interior of the liposomes. Coating with chitosan did not change the polyphenol content in the liposomes (86.6%). The uncoated liposomes without grape seed extract were highly prone to lipid oxidation. The cationic chitosan coating, however, improved the oxidative stability to some extent, due to its ability to repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant activity in both primary and secondary liposomes, which may be attributed to its polyphenol content. In conclusion, the best chemical stability of liposomes can be achieved using a combination of grape seed extract and chitosan. Full article
(This article belongs to the Special Issue Liposome Technologies)
Open AccessArticle The Flux of Phenolic Compounds through Silicone Membranes
Pharmaceutics 2013, 5(3), 434-444; doi:10.3390/pharmaceutics5030434
Received: 11 July 2013 / Revised: 14 August 2013 / Accepted: 14 August 2013 / Published: 21 August 2013
Cited by 3 | PDF Full-text (340 KB) | HTML Full-text | XML Full-text
Abstract
Phenols as a class of molecules have been reported to exhibit higher log maximum fluxes through human stratum corneum, SC, from water, log JMHAQ, than other classes of molecules. This suggests that their corresponding log maximum fluxes through silicone from [...] Read more.
Phenols as a class of molecules have been reported to exhibit higher log maximum fluxes through human stratum corneum, SC, from water, log JMHAQ, than other classes of molecules. This suggests that their corresponding log maximum fluxes through silicone from water, log JMPAQ, may be useful to extend the existing n = 63 log JMPAQ database to include more log JMPAQ values greater than 0.0. The log JMPAQ values for n = 7 phenols predicted to give log JMPAQ values greater than 0.0 based on their log JMHAQ values have been experimentally determined. These n = 7 new log JMPAQ values have been added to the existing n = 63 log JMPAQ database to give a new n = 70 database and the n = 7 literature log JMHAQ values have been added to the existing n = 48 log JMHAQ database (matched to the n = 63 log JMPAQ database) to give a new n = 55 database. The addition of the n = 7 phenols improved the correlations of these flux databases when fitted to the Roberts-Sloan equation, RS, as well as the correlation between the matched experimental (Exp.) log JMPAQ with the Exp. log JMHAQ. Full article
(This article belongs to the Special Issue Advanced Transdermal Drug Delivery)
Open AccessArticle Pectosomes and Chitosomes as Delivery Systems for Metronidazole: The One-Pot Preparation Method
Pharmaceutics 2013, 5(3), 445-456; doi:10.3390/pharmaceutics5030445
Received: 16 August 2013 / Revised: 29 August 2013 / Accepted: 4 September 2013 / Published: 6 September 2013
Cited by 5 | PDF Full-text (696 KB) | HTML Full-text | XML Full-text
Abstract
Mucoadhesive liposomes offer a potential for improved residence time of liposomal systems targeting contact with mucosal tissues, such as in buccal, oral, colon, and vaginal drug delivery. Most of the currently available methods rely on the coating of preformed liposomes by various [...] Read more.
Mucoadhesive liposomes offer a potential for improved residence time of liposomal systems targeting contact with mucosal tissues, such as in buccal, oral, colon, and vaginal drug delivery. Most of the currently available methods rely on the coating of preformed liposomes by various mucoadhesive polymers. The aim of this study was to develop novel mucoadhesive system by the one-pot preparation method. The pectin- and chitosan-containing liposomes, namely pectosomes and chitosomes, were prepared by the modified solvent injection method. In order to optimize this novel delivery system, we used pectins and chitosans of both high and low degree of esterification/deacetylation (DE/DD), respectively. Sonication was applied to reduce the original vesicle size. All vesicles were characterized for their size, zeta potential, metronidazole entrapment, and stability. Both pectosomes and chitosomes were found to entrap more metronidazole than conventional plain liposomes. Preliminary data indicate that the polymer is present on the liposomal surface, embedded within inner liposomal bilayers, and entrapped inside the aqueous compartment. The next step in the evaluation of this system is the testing of its mucoadhesiveness. Full article
(This article belongs to the Special Issue Liposome Technologies)
Figures

Review

Jump to: Research

Open AccessReview New Transfection Agents Based on Liposomes Containing Biosurfactant MEL-A
Pharmaceutics 2013, 5(3), 411-420; doi:10.3390/pharmaceutics5030411
Received: 27 June 2013 / Revised: 29 July 2013 / Accepted: 8 August 2013 / Published: 16 August 2013
PDF Full-text (493 KB) | HTML Full-text | XML Full-text
Abstract
Nano vectors are useful tools to deliver foreign DNAs, oligonucleotides, and small interfering double-stranded RNAs (siRNAs) into mammalian cells with gene transfection and gene regulation. In such experiments we have found the liposomes with a biosurfacant mannosylerythriol lipid (MEL-A) are useful because [...] Read more.
Nano vectors are useful tools to deliver foreign DNAs, oligonucleotides, and small interfering double-stranded RNAs (siRNAs) into mammalian cells with gene transfection and gene regulation. In such experiments we have found the liposomes with a biosurfacant mannosylerythriol lipid (MEL-A) are useful because of their high transfer efficiency, and their unique mechanism to transfer genes to target cells with the lowest toxicity. In the present review we will describe our current work, which may contribute to the great advance of gene transfer to target cells and gene regulations. For more than two decades, the liposome technologies have changed dramatically and various methods have been proposed in the fields of biochemistry, cell biology, biotechnology, and so on. In addition, they were towards to pharmaceutics and clinical applications. The liposome technologies were expected to use gene therapy, however, they have not reached a requested goal as of yet. In the present paper we would like to present an approach using a biosurfactant, MEL-A, which is a surface-active compound produced by microorganisms growing on water-insoluble substrates and increases efficiency in gene transfection. The present work shows new transfection agents based on liposomes containing biosurfactant MEL-A. Full article
(This article belongs to the Special Issue Liposome Technologies)
Open AccessReview Bioavailability of Polyphenol Liposomes: A Challenge Ahead
Pharmaceutics 2013, 5(3), 457-471; doi:10.3390/pharmaceutics5030457
Received: 1 August 2013 / Revised: 29 August 2013 / Accepted: 4 September 2013 / Published: 17 September 2013
Cited by 15 | PDF Full-text (332 KB) | HTML Full-text | XML Full-text
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 few years, a [...] Read more.
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 few 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 of 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 are suggested. Full article
(This article belongs to the Special Issue Liposome Technologies)
Open AccessReview Proteoliposomes as Tool for Assaying Membrane Transporter Functions and Interactions with Xenobiotics
Pharmaceutics 2013, 5(3), 472-497; doi:10.3390/pharmaceutics5030472
Received: 23 July 2013 / Revised: 15 August 2013 / Accepted: 4 September 2013 / Published: 18 September 2013
Cited by 10 | PDF Full-text (826 KB) | HTML Full-text | XML Full-text
Abstract
Proteoliposomes represent a suitable and up to date tool for studying membrane transporters which physiologically mediate absorption, excretion, trafficking and reabsorption of nutrients and metabolites. Using recently developed reconstitution strategies, transporters can be inserted in artificial bilayers with the same orientation as [...] Read more.
Proteoliposomes represent a suitable and up to date tool for studying membrane transporters which physiologically mediate absorption, excretion, trafficking and reabsorption of nutrients and metabolites. Using recently developed reconstitution strategies, transporters can be inserted in artificial bilayers with the same orientation as in the cell membranes and in the absence of other interfering molecular systems. These methodologies are very suitable for studying kinetic parameters and molecular mechanisms. After the first applications on mitochondrial transporters, in the last decade, proteoliposomes obtained with optimized methodologies have been used for studying plasma membrane transporters and defining their functional and kinetic properties and structure/function relationships. A lot of information has been obtained which has clarified and completed the knowledge on several transporters among which the OCTN sub-family members, transporters for neutral amino acid, B0AT1 and ASCT2, and others. Transporters can mediate absorption of substrate-like derivatives or drugs, improving their bioavailability or can interact with these compounds or other xenobiotics, leading to side/toxic effects. Therefore, proteoliposomes have recently been used for studying the interaction of some plasma membrane and mitochondrial transporters with toxic compounds, such as mercurials, H2O2 and some drugs. Several mechanisms have been defined and in some cases the amino acid residues responsible for the interaction have been identified. The data obtained indicate proteoliposomes as a novel and potentially important tool in drug discovery. Full article
(This article belongs to the Special Issue Liposome Technologies)
Open AccessReview Advances in Lipid Nanoparticles for siRNA Delivery
Pharmaceutics 2013, 5(3), 498-507; doi:10.3390/pharmaceutics5030498
Received: 1 July 2013 / Revised: 4 September 2013 / Accepted: 12 September 2013 / Published: 18 September 2013
Cited by 25 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
Technological advances in both siRNA (small interfering RNA) and whole genome sequencing have demonstrated great potential in translating genetic information into siRNA-based drugs to halt the synthesis of most disease-causing proteins. Despite its powerful promises as a drug, siRNA requires a sophisticated [...] Read more.
Technological advances in both siRNA (small interfering RNA) and whole genome sequencing have demonstrated great potential in translating genetic information into siRNA-based drugs to halt the synthesis of most disease-causing proteins. Despite its powerful promises as a drug, siRNA requires a 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 nanoparticle (LNP) containing ionizable amino lipids is the leading delivery technology for siRNA, with five products in clinical trials and more in the pipeline. Here, we focus on the technological advances behind these potent systems for siRNA-mediated gene silencing. Full article
(This article belongs to the Special Issue Liposome Technologies)

Journal Contact

MDPI AG
Pharmaceutics Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
pharmaceutics@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Pharmaceutics
Back to Top