Lizelle T. Fox

Transdermal drug delivery enhancement by compounds of natural origin

The transdermal route of administration offers an alternative pathway for systemic drug delivery with numerous advantages over conventional routes. Regrettably, the stratum corneum forms a formidable barrier that hinders the percutaneous penetration of most drugs, offering an important protection mechanism to the organism against entrance of possible dangerous exogenous molecules. Different types of penetration enhancers have shown the potential to reversibly overcome this barrier to provide effective delivery of drugs across the skin. Although certain chemical and physical skin penetration enhancers are already employed by the pharmaceutical industry in commercially available transdermal products, some skin penetration enhancers are associated with irritating and toxic effects. This emphasizes the need for the discovery of new, safe and effective skin penetration enhancers. Penetration enhancers from natural origin have become popular as they offer several benefits over their synthetic counterparts such as sustainable mass production from a renewable resource and lower cost depending on the type of extraction used. The aim of this article is to give a comprehensive summary of the results from scientific research conducted on skin penetration enhancers of natural origin. The discussions on these natural penetration enhancers have been organized into the following chemical classes: essential oils, terpenes, fatty acids and polysaccharides.

Topical delivery of acyclovir and ketoconazole

Abstract Context: Viral and fungal cutaneous manifestations are regularly encountered in immunocompromised human immunodeficiency virus/acquired immunodeficiency syndrome individuals and can be treated by drugs such as acyclovir and ketoconazole, respectively. Objective: The aim of this study was to determine whether the novel Pheroid™ delivery system improved the transdermal delivery and/or dermal delivery of acyclovir and ketoconazole when incorporated into semi-solid formulations. Materials and methods: Semi-solid products (creams and emulgels) containing these drug compounds were formulated, either with or without (control) the Pheroid™ delivery system. The stability of the formulated semi-solid products was examined over a period of six months and included the assay of the actives, pH, viscosity, mass loss and particle size observation. Vertical Franz cell diffusion studies and tape stripping methods were used to determine the in vitro, stratum corneum (SC)-epidermis and epidermis-dermis delivery of these formulations. Results and discussion: Stability tests showed that none of the formulations were completely stable. Acyclovir showed a biphasic character during the in vitro skin diffusion studies for all the tested formulations. The Pheroid™ cream enhanced the transdermal, SC-epidermis and epidermis–dermis delivery of acyclovir the most. The average amount of ketoconazole diffused over 12 h showed improved delivery of ketoconazole, with the Pheroid™ emulgel exhibiting the best transdermal and epidermis–dermis delivery. Conclusion: The Pheroid™ formulae increased transdermal penetration as well as delivery to the dermal and epidermal skin layers. The Pheroid™ emulgel and the Pheroid™ cream increased the topical delivery of ketoconazole and acyclovir, respectively.

Treatment Modalities for Acne.

Acne is a common inflammatory skin disease which affects the pilosebaceous units of the skin. It can have severe psychological effects and can leave the patient with severe skin scarring. There are four well-recognized pathological factors responsible for acne which is also the target for acne therapy. In this review, different treatment options are discussed, including topical (i.e., retinoids, and antibiotics) and systemic (i.e., retinoids, antibiotics, and hormonal) treatments. Since the general public has been showing an increasing interest in more natural and generally safer treatment options, the use of complementary and alternative medicines (CAM) for treating acne was also discussed. The use of physical therapies such as comedone extraction, cryoslush therapy, cryotherapy, electrocauterization, intralesional corticosteroids and optical treatments are also mentioned. Acne has been extensively researched with regards to the disease mechanism as well as treatment options. However, due to the increasing resistance of Propionibacterium acnes towards the available antibiotics, there is a need for new treatment methods. Additionally, the lack of necessary evidence on the efficacy of CAM therapies makes it necessary for researchers to investigate these treatment options further.

In Vivo skin hydration and anti-erythema effects of Aloe vera, Aloe ferox and Aloe marlothii gel materials after single and multiple applications

Objective: To investigate the skin hydrating and anti-erythema activity of gel materials from Aloe marlothii A. Berger and A. ferox Mill. in comparison to that of Aloe barbadensis Miller (Aloe vera) in healthy human volunteers. Materials and Methods: Aqueous solutions of the polisaccharidic fractions of the selected aloe leaf gel materials were applied to the volar forearm skin of female subjects. The hydration effect of the aloe gel materials were measured with a Corneometer® CM 825, Visioscan® VC 98 and Cutometer® dual MPA 580 after single and multiple applications. The Mexameter® MX 18 was used to determine the anti-erythema effects of the aloe material solutions on irritated skin areas. Results: The A. vera and A. marlothii gel materials hydrated the skin after a single application, whereas the A. ferox gel material showed dehydration effects compared to the placebo. After multiple applications all the aloe materials exhibited dehydration effects on the skin. Mexameter® readings showed that A. vera and A. ferox have anti-erythema activity similar to that of the positive control group (i.e. hydrocortisone gel) after 6 days of treatment. Conclusion: The polysaccharide component of the gel materials from selected aloe species has a dehydrating effect on the skin after multiple applications. Both A. vera and A. ferox gel materials showed potential to reduce erythema on the skin similar to that of hydrocortisone gel.

In vitro wound healing and cytotoxic activity of the gel and whole-leaf materials from selected aloe species

ETHNOPHARMACOLOGICAL RELEVANCE Aloe vera is one of the most important medicinal plants in the world with applications in the cosmetic industry and also in the tonic or health drink product market. Different parts of Aloe ferox and Aloe marlothii are used as traditional medicines for different applications. Although wound healing has been shown for certain aloe gel materials (e.g. A. vera ) previously, there are conflicting reports on this medicinal application of aloe leaf gel materials. AIM OF THE STUDY The present study aimed at determining the wound healing properties of the gel and whole-leaf materials of Aloe vera, Aloe ferox and Aloe marlothii, as well as their cytotoxic effects on normal human keratinocyte cells (HaCaT). MATERIALS AND METHODS Nuclear magnetic resonance spectroscopy was used to chemically fingerprint the aloe gel and whole-leaf materials by identifying characteristic marker molecules of aloe gel and whole-leaf materials. An MTT assay was performed to determine the cytotoxicity of the various aloe whole-leaf and gel materials on HaCaT cells. Wound healing and in vitro cell migration were investigated with HaCaT cells by means of the CytoSelect™ assay kit. RESULTS The in vitro wound healing assay suggested that all the aloe gel and whole-leaf materials examined, exhibited faster wound healing activity than the untreated control group. After 48h, all the aloe gel and whole-leaf materials almost completely caused full wound closure, displaying 98.07% (A. marlothii whole-leaf), 98.00% (A. vera gel), 97.20% (A. marlothii gel), 96.00% (A. vera whole-leaf), 94.00% (A. ferox gel) and 81.30% (A. ferox whole-leaf) wound closure, respectively. It was noteworthy that the gel materials of all the three aloe species exhibited significantly faster (p<0.05) wound healing actions when compared to their respective whole-leaf materials at 32h. CONCLUSION The gel and whole-leaf materials of A. vera, A. ferox and A. marlothii have shown the ability to heal wounds at a faster rate and to a larger extent than untreated keratinocytes. The MTT assay results suggested that the gel and whole-leaf materials of all the selected Aloe species showed negligible toxicity towards the HaCaT cells.

Skin permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox

The aim of this study was to investigate the in‐vitro permeation enhancement effects of the gel and whole‐leaf materials of Aloe vera, Aloe marlothii and Aloe ferox using ketoprofen as a marker compound.

Topical and transdermal delivery of L-carnitine.

Background: The two types of skin aging (intrinsic and extrinsic) share important molecular features, while having distinct differences on the macromolecular level: both lead to increased production of reactive oxygen species, enhanced matrix metalloproteinase expression and decreased procollagen synthesis. L-Carnitine L-tartrate has been reported to have anti-aging effects. Aim and Methods: The delivery as well as the transport of L-carnitine to the target sites, i.e. stratum corneum and epidermis-dermis of female abdominal skin, with and without the use of Pheroid™ as delivery system, were investigated during this study by use of Franz diffusion cells and analysed by liquid chromatography/mass spectrometry. The presence of endogenous L-carnitine in human skin was also investigated. Results and Conclusion: The Pheroid™ delivery system enhanced the diffusion of L-carnitine through the skin, although the phosphate buffer solution (PBS) showed a higher concentration of the active agent in the skin layers. This could be because Pheroid, being more lipophilic than PBS, improved the diffusion of L-carnitine through the skin layers, consequently leading to a lesser amount of L-carnitine delivered to the target site, i.e. the epidermis-dermis.

In vitro skin permeation of artemisone and its nano-vesicular formulations

The artemisinin derivative artemisone has antitumor activity. In particular when encapsulated in solid lipid nanoparticles (SLNs) and niosomes, it is active against human melanoma A-375 cells, although such formulations have a negligible effect on human keratinocyte cells. The aim here was to determine whether these formulations could enhance the topical delivery and skin permeation of artemisone as a prelude to evaluating use of artemisone and related compounds for melanoma treatment. In vitro skin permeation studies were conducted to determine the concentration of artemisone delivered into the stratum corneum-epidermis and epidermis-dermis. Artemisone-SLNs delivered artemisone into the stratum corneum-epidermis at significantly higher concentration (62.632 μg/mL) than the artemisone-niosomes (12.792 μg/mL). Neither of the controls delivered artemisone into the stratum corneum-epidermis. In the epidermis-dermis, artemisone (13.404 μg/mL) was only detected after application of the SLN formulation. Overall, the excellent topical delivery of artemisone with the SLN formulation coupled with the intrinsic activity of formulated artemisone confirms potential for use in treatment of melanoma.

In vitro skin permeation of sinigrin from its phytosome complex

Sinigrin is a major glucosinolate present in plants of the Brassicaceae family. Recently, sinigrin and its phytosome formulations have been investigated for its wound‐healing actions, by our research group. The aim of this study was to demonstrate sinigrin drug release from its phytosome complex and also to determine whether the phytosome complex enhances the delivery of sinigrin into the skin when compared to free sinigrin.

Vesicular Carriers for Skin Drug Delivery: The Pheroid™ Technology

The skin remains an attractive area for drug delivery. The skin, however, often limits the ingress of drugs, because of its very low permeability. Much research, focusing on employing a variety of physical and chemical methods, aimed at reversibly altering skin permeability in favour of compounds, has been reported. Of the many chemical approaches that exist, one comprises the use of vesicular carriers for delivering drugs into and possibly through the skin. This review offers an overview of various vesicles that have been investigated during dermal and transdermal drug delivery research in recent years, with special emphasis on a relatively new carrier, namely the Pheroid™. The progress made to date by our research group with regards to the use of the Pheroid™ as transdermal delivery vector, is also discussed in detail.