Myeong Jun Choi

Liposomes and Niosomes as Topical Drug Delivery Systems

The skin acts as a major target as well as a principle barrier for topical/transdermal (TT) drug delivery. The stratum corneum plays a crucial role in barrier function for TT drug delivery. Despite major research and development efforts in TT systems and the advantages of these routes, low stratum corneum permeability limits the usefulness of topical drug delivery. To overcome this, methods have been assessed to increase permeation. One controversial method is the use of vesicular systems, such as liposomes and niosomes, whose effectiveness depends on their physicochemical properties. This review focuses on the effect of liposomes and niosomes on enhancing drug penetration, and defines the effect of composition, size and type of the vesicular system on TT delivery.

Role of Ceramides in Barrier Function of Healthy and Diseased Skin

Stratum corneum intercellular lipids play an important role in the regulation of skin water barrier homeostasis and water-holding capacity. Modification of intercellular lipid organization and composition may impair these properties. Patients with skin diseases such as atopic dermatitis, psoriasis, contact dermatitis, and some genetic disorders have diminished skin barrier function. Lipid composition in diseased skin is characterized by decreased levels of ceramide and altered ceramide profiles. To clarify mechanisms underlying ceramides as a causative factor of skin disease, investigators have examined the activity of enzymes in the stratum corneum on ceramide production and degradation. The activities of ceramidase, sphingomyelin deacylase, and glucosylceramide deacylase are increased in epidermal atopic dermatitis. Investigators have also compared the expression levels of sphingolipid activator protein in the epidermis of normal and diseased skin. A decreased level of prosaposin has been identified in both atopic dermatitis and psoriasis. These results indicate that decreased ceramide level is a major etiologic factor in skin diseases. Hence, topical skin lipid supplementation may provide opportunities for controlling ceramide deficiency and improving skin condition.

Elastic vesicles as topical/transdermal drug delivery systems

Skin acts a major target as well as a principle barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Elastic vesicles are classified with phospholipid (Transfersomes® and ethosomes) and detergent‐based types. Elastic vesicles were more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. Their effectiveness strongly depends on their physicochemical properties: composition, duration and application volume, and entrapment efficiency and application methods. This review focuses on the effect of elastic liposomes for enhancing the drug penetration and defines the action mechanism of penetration into deeper skin.

Topical vaccination of DNA antigens: Topical delivery of DNA antigens

Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune responses in vivo. The skin is an attractive site for the delivery of DNA antigens for DNA vaccination. However, due to skin’s barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability, chemical and physical approaches have been examined to decrease stratum corneum barrier properties. Topical vaccination has been achieved using topical application of naked DNA, DNA/liposomes or emulsion complex, liposomal cream, as well as physical methods such as stripping, electroporation, and micromechanical disruption methods. All methods resulted in a significant enhancement in humoral and cellular immune responses over naked DNA alone. To develop more cost-effective and needle-free vaccines, skin-targeted immunizations are required. This review focuses on the chemical and physical methods developed to enhance DNA delivery into skin.

Topical DNA vaccination with DNA/Lipid based complex.

Topical DNA vaccines have been shown to elicit both broad humoral and cellular immune response in vivo. The skin is an attractive site for the delivery DNA antigens for DNA vaccination. However, due to skins barrier properties, the penetration of DNA and the applications of topical vaccination are limited. To improve permeability of stratum corneum and the potency of topical DNA vaccines, efficient delivery systems are needed. Topical vaccination has been achieved using topical application of naked DNA with or without tape stripping and DNA/lipid based complex such as liposomes, niosomes, Transfersomes, or microemulsion. All methods resulted in significant enhancement in humoral and cellular immune response over naked DNA alone. To develop more cost-effective and needle free vaccines, skin targeted immunizations are required. This overview focuses on the comparison of the potency of topical DNA vaccine between naked DNA and DNA-lipid based complex.

Evaluation of the Antioxidant Capacity and Preventive Effects of a Topical Emulsion and Its Vehicle Control on the Skin Response to UV Exposure

Supplying topical exogenous antioxidants to the skin may prevent or minimize free radical-induced damaging. This study determines antioxidative capacity of a topical skin care emulsion (an oil-in-water vitamin E-containing formulation) versus its vehicle on human skin that was exposed to ultraviolet radiation (UVR) by utilizing a photochemiluminescence device and biophysical methods. Ten healthy Caucasians (3 male and 7 female; mean age 47 ± 10 years) were enrolled. In a randomized and double-blind manner, a pH-balanced vitamin E emulsion or its vehicle control was applied onto predesignated forearm prior to UVR exposure. Thirty minutes after application, these test sites were exposed to a UV light to induce the minimal erythema dose. One untreated site served as a blank control. Visual scoring and instrumental measurements were recorded at baseline and at 24 h and 48 h thereafter. At day 3, after completing instrumental measurements, each test site was stripped three times in a consecutive manner with a proprietary adhesive tape disc. These tapes were quantified for antioxidant capacity using a photochemiluminescence device.Vitamin E emulsion and vehicle control significantly (p < 0.05) suppressed visual scores when compared with blank control at day 2 and day 3 after UV exposure. However, vitamin E emulsion showed significantly (p < 0.05) lower visual scores when compared with vehicle control at day 2 and day 3 after UV exposure.Also,vitamin E emulsion and its vehicle control significantly (p < 0.05) diminished skin color measurement (a*) values when compared with blank control at day 2 and day 3 after UV exposure. At day 2 after UV exposure, only vitamin E emulsion significantly (p < 0.05) reduced skin blood flow volume when compared with blank control. Vitamin E emulsion and its vehicle control showed significant (p < 0.05) reduction of blood flow volume when compared with blank control at day 3 after UV exposure. Vitamin E emulsion and its vehicle control proved effective in preventing induction of erythema and reducing inflammatory damage caused by UV exposure. The effect of vitamin E emulsion exceeded that of an ‘active control’.

Effect of Tape Stripping on Percutaneous Penetration and Topical Vaccination

The stratum corneum provides the first barrier to the percutaneous absorption of drugs as well as regulating water loss. This barrier limits the topical/transdermal delivery of drugs and biological macromolecules. Chemical and physical approaches have been examined to decrease these properties. Tape stripping is commonly used to disrupt the epidermal barrier, to enhance the delivery of drugs and to obtain information about stratum corneum function. Tape stripping results in the production and release of cytokines and co-stimulatory molecules and increases the humoral and cellular immune responses against peptide, protein and DNA antigens by a topical vaccination in vivo. This paper reviews the stripping method, experimental factors and its applications for penetration and topical vaccination.

A rapid, accurate, and facile method to quantify the antioxidative capacity of topical formulations.

Background/aims: Various methodologies have been developed to quantify antioxidant activity. A simple, rapid and accurate method is demanded. This study examined the antioxidative status of a pH balanced vitamin E containing formulation versus its vehicle control utilizing a photochemiluminescence device.

Role of Ceramides in Skin Stress: Ultraviolet Light, Tape Stripping and Crowding

Stratum corneum intercellular lipids regulate skin water barrier function and water-holding capacity; their modification may impair these properties. Physical and chemical stresses diminish barrier function. Acute barrier disruption by tape stripping increases sphingomyelinase and serine palmitoyltransferase activity; ceramide contents are increased to restore barrier function. Overcrowding stress induces dry skin, and the barrier function impairment correlates with decreased skin cera- mides. The effect of UV irradiation on ceramide content and barrier function varies with doses and UV wavelength. Stress-induced ceramide generation may induce apoptosis in cultured human keratinocytes and restore barrier function. This review focuses on the role of ceramides in physical and chemical stress, suggesting that refinement and extension of this academic domain may lead to therapeutic advances.