Liposomes — microscopic phospholipid bubbles with a bilayered membrane structure — have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs — from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.

Recent advances with liposomes as pharmaceutical carriers.

Liposomal drug delivery systems: from concept to clinical applications.

Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives

PLGA-based nanoparticles: An overview of biomedical applications

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.

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Transdermal drug delivery

The aim of this work was to generate a tunable surface isoelectric point (sIEP), where the surface is modified with two molecules: a weak base (pyridine), carrying a pH dependent positive charge, and a derivative of a strong acid (sulfate), carrying a permanent negative charge in a physiologically relevant pH range. To this end, silicon surfaces were modified with 3-aminopropyltriethoxysilane. These amine-modified surfaces were subsequently derivatized into pyridine- or sulfate-modified surfaces. Then, the surface pKa of pyridine-modified surfaces was determined by a fluorescent nanoparticle adhesion assay (FNAA). Next, these values were used to calculate in which ratio the chemicals must be present in the reaction mixture to generate a mixed pyridine/sulfate-modified surface with a target sIEP. After preparing surfaces with a target sIEP, an FNAA with positively and negatively charged nanoparticles was used to verify the sIEP of the generated surfaces. The FNAA revealed that pyridine-modified surfaces had a pKa of 6.69 ± 0.18. When an sIEP was generated, negative nanoparticles bound to surfaces at pH values below the sIEP and positive nanoparticles bound at pH values above the sIEP. Furthermore, we found sIEP values of 5.97 ± 0.88 when we aimed for an sIEP of 6.2, and 7.12 ± 0.21 when we aimed for an sIEP of 7.1. Finally, the pH dependent binding and release of a negatively and positively charged (bio)polymer was investigated for a target sIEP of 7. A negatively charged polymer (poly(I:C)) was bound at a pH sIEP with a release efficiency of 85 ± 9% and a positively charged polymer (trimethyl chitosan) bound at a pH > sIEP and released at a pH < sIEP with a release efficiency of 72 ± 9%. In conclusion, we established a method for preparing modified silicon surfaces with a tunable sIEP, which can be used for pH-dependent binding and release of biomacromolecules.

Chemical modifications of silicon surfaces for the generation of a tunable surface isoelectric point

The use of high-sensitivity differential scanning calorimetry to characterise dilute aqueous dispersions of surfactants

Properties of mixed crystalline organic material prepared by zone levelling III. Vapour pressures of (trans-azobenzene + trans-stilbene)

Purpose. To study at the ultrastructural level which part of the skin is associated with percutaneous iodide transport by passive diffusion and iontophoresis.

X-ray microanalysis of cryopreserved human skin to study the effect of iontophoresis on percutaneous ion transport.

The skin acts as an effective barrier to protect the body against penetration of substances from the environment and against desiccation The main barrier function resides in the stratum corneum, and more specifically in the intercellular lipid domains Several techniques have been used to elucidate the local lipid crystal arrangements in these domains, but they either needed an extensive pretreatment of the skin with the risk of damaging the native structure, or were not suited to obtain local structure information as bulk quantities of stratum corneum were required In this paper a method of performing local structure analysis (electron diffraction) on cryo-fixed specimens is described Therefore a cold chain procedure was used to obtain cryosections of stratum corneum On these sections visualization and electron diffraction at low temperature were carried out



Using a so-called tape sandwich method, cryosections were prepared in which corneocytes and lipid matrix could easily be distinguished Moreover, detailed cellular components such as desmosomes and intracellular lipid domains were observed However, probably due to the limited amount of intercellular lipids in the stratum corneum, electron diffraction on cryosections did not result in diffraction patterns that were undoubtedly originating from the intercellular lipids In the electron diffraction patterns of a skin lipid model system reflections were present that were indicative of hexagonal and orthorhombic sublattices The d-spacings of these reflections were similar to the spacings of the high-intensity reflections of the X-ray diffraction pattern of the same mixture This showed agreement between a bulk and a local technique, X-ray and electron diffraction

Joke A. Bouwstra

Papers

Chemical modifications of silicon surfaces for the generation of a tunable surface isoelectric point

The use of high-sensitivity differential scanning calorimetry to characterise dilute aqueous dispersions of surfactants

Properties of mixed crystalline organic material prepared by zone levelling III. Vapour pressures of (trans-azobenzene + trans-stilbene)

X-ray microanalysis of cryopreserved human skin to study the effect of iontophoresis on percutaneous ion transport.

Visualization and electron diffraction on cryosections of stratum corneum: a utopia?