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

Free fatty acids chain length distribution affects the permeability of skin lipid model membranes.

The lipid matrix in the stratum corneum (SC), the upper layer of the skin, plays a critical role in the skin barrier. The matrix consists of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). In human SC, these lipids form two coexisting crystalline lamellar phases with periodicities of approximately 6 and 13 nm. In the studies reported here, we investigated the effect of CHOL on lipid organization in each of these lamellar phases separately. For this purpose, we used lipid model mixtures. Our studies revealed that CHOL is imperative for the formation of each of the lamellar phases. At low CHOL levels, the formation of the lamellar phases was dramatically changed: a minimum 0.2 CHOL level in the CER/CHOL/FFA (1 : 0.2 : 1) mixture is required for the formation of each of the lamellar phases. Furthermore, CHOL enhances the formation of the highly dense orthorhombic lateral packing. The gradual increment of CHOL increases the fraction of lipids forming the very dense orthorhombic lateral packing. Therefore, these studies demonstrate that CHOL is an indispensable component of the SC lipid matrix and is of fundamental importance for appropriate dense lipid organization and thus important for the skin barrier function.

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Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization

Two new methods for preparing a unique stratum corneum substitute.

The freezing and melting behavior of water in poly hydroxy ethyl methacrylate (pHEMA) hydrogels of different cross-linker and water contents was investigated in relation to the glass transition temperature (Tg) of the gels. After prolonged cooling at −15°C a constant amount of 1.7 mol water per monomeric unit did not freeze, regardless of both the cross-linker and the water content of the gels. At this water content and temperature, pHEMA gels were below their Tg, and the water molecules were prevented from diffusing to the ice crystals formed in the gel. Therefore, the inability of part of the water in pHEMA gels to freeze is not a thermodynamic phenomenon but is caused by kinetic factors.

Thermal Behavior of Poly Hydroxy Ethyl Methacrylate (pHEMA) Hydrogels

Purpose
To determine the immunogenicity of diphtheria toxoid (DT) formulated in two types of vesicles following transcutaneous immunization (TCI) of mice onto microneedle array-treated skin.

https://link.springer.com/content/pdf/10.1007%2Fs11095-010-0093-y.pdf

Joke A. Bouwstra

Papers

Free fatty acids chain length distribution affects the permeability of skin lipid model membranes.

Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization

Two new methods for preparing a unique stratum corneum substitute.

Thermal Behavior of Poly Hydroxy Ethyl Methacrylate (pHEMA) Hydrogels

Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array