Transdermal penetration enhancement and clinical efficacy of Aloe marlothii and Aloe ferox compared to Aloe vera
Fox, Lizelle Trifena
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Extensive research has already been performed on Aloe vera therefore it is important that researchers include other aloe species, such as Aloe marlothii and Aloe ferox, in studies involving aloe plant materials (Loots et al., 2007:6891). The use of natural products has regained popularity and in recent years the demand for alternative medication has risen considerably (Walji & Wiktorowicz, 2013:86). The hydration state of the human skin is fundamental for its normal functioning (Verdier-Sévrain & Bonté, 2007:75), with healthy skin possessing a water content higher than 10% (w/v) (Blank, 1952:439). This demonstrates the importance of the topical application of skin moisturisers as part of basic skin care regime (Verdier-Sévrain & Bonté, 2007:75). The first part of this project focused on the in vivo skin hydration effects of the precipitated polysaccharide components of A. vera, A. ferox and A. marlothii leaf gel materials (3% (w/v)) after single (30, 90 and 150 min after application) and multiple applications (twice daily application over a period of four weeks) on healthy volunteers, respectively. The anti-erythema effects of these aloe materials on sodium lauryl sulphate irritated skin were also examined. The skin hydration effects of the aloe materials were determined with the Corneometer® CM 825 and Visioscan® VC 98 during the short term study (single application) and longer term study (multiple applications). In addition, as an indirect measurement of skin hydration, the Cutometer® dual MPA 580 was used to measure skin elasticity during the longer term study. To determine the anti-erythema effects of the aloe materials when applied to irritated skin areas, the haemoglobin content of the skin was measured with a Mexameter® MX 18. The results from the in vivo study indicated that A. ferox gel material dehydrated the skin, whereas A. vera and A. marlothii gel materials hydrated the skin during the short term study. Results from the longer term study showed that all the aloe leaf materials have skin dehydration effects, probably due to the aloe absorbing moisture from the skin into the applied gel layer upon drying. From the anti-erythema study, it was seen that A. vera and A. ferox materials had the potential to reduce erythema on the skin similar to that of the positive control group (i.e. hydrocortisone gel) after six days of treatment. The skin possesses exceptional barrier properties which can mostly be ascribed to the outermost layer of the skin, the stratum corneum (SC). Due to the physical barrier the skin has against drug permeation, the delivery of drug molecules into and across the skin continues to be challenging (Lane, 2013:13) and to overcome this barrier, penetration enhancers can be used to efficiently deliver drugs across the skin (Barry, 2002:522). The aim of the second part of this project was to determine the skin penetration enhancing effects of the gel and whole leaf materials of A. vera, A. marlothii and A. ferox. Ketoprofen was used as the marker compound and a high performance liquid chromatography (HPLC) method was developed and validated to determine the amount of ketoprofen present in the samples. Prior to the skin diffusion studies, membrane release studies were performed to test whether the solutions containing different concentrations of the aloe leaf materials (i.e. 3.00%, 1.50% and 0.75% (w/v)) released ketoprofen from their gel-like structures. From these studies, it was evident the 0.75% (w/v) concentration had the highest average percentage ketoprofen release, which was subsequently chosen as the concentration for the aloe leaf materials tested in the transdermal skin diffusion studies. The in vitro permeation study was conducted across dermatomed (400 μm thick) skin in Franz diffusion cells. Tape stripping was performed after completion of the diffusion studies to determine the concentration ketoprofen present in the SC-epidermis and epidermis-dermis layers of the skin. Results from the in vitro permeation study showed that A. vera gel enhanced the flux of ketoprofen to the highest extent (20.464 μg/cm2.h) when compared to the control group (8.020 μg/cm2.h). Aloe marlothii gel (12.756 μg/cm2.h) and A. ferox whole leaf material (12.187 μg/cm2.h) also enhanced the permeation of ketoprofen across the skin compared to the control group. A. vera gel material was the most efficient transdermal drug penetration enhancer of the selected aloe species investigated. In order to determine by which mechanism the aloe leaf materials enhanced the skin permeation of ketoprofen (Hadgraft et al., 2003:141), the permeation profiles were analysed using a non-linear curve-fitting procedure (Díez-Sales et al., 1991:3) to obtain α, β and kp values. A change in the α-value indicated the aloe leaf material influenced the partition coefficient (K), whereas a change in β indicated the aloe leaf material influenced the diffusivity (D) (with the assumption that h, the diffusional path length is constant) (Otto et al., 2010:278).The calculated α-values indicated the drug permeation enhancing effect of A. vera gel can be ascribed to an increased partitioning of the drug into the skin. The calculated β-values showed A. ferox whole leaf altered the diffusion characteristics of the skin for ketoprofen. The tape stripping results showed A. marlothii whole leaf delivered the highest concentration of the ketoprofen into the SC-epidermis and epidermis-dermis layers of the skin.
- Health Sciences