Reliability of a standardized tool for evaluating severity of cellulite in the female posterior thigh.

Numerous products and minimally-invasive procedures are available to reduce cellulite. However, there are a limited number of tools to evaluate the effects of these interventions and some are relatively complex to implement. OBJECTIVE: This study evaluated the reliability of a standardized grading system for scoring the overall severity of cellulite on the posterior thigh. The study evaluated inter-rater and intra-rater (test/re-test) reliability of the method and engaged in an iterative process to develop a reliable method to evaluate changes in the appearance of cellulite. METHODS: There were two stages in the validation process. The first stage was an open process without evaluator training. The second stage was a more controlled process with training given and moderator involvement to review grade selections. In the first stage, inter-rater reliability was examined across five evaluators who were asked to evaluate 24 photographs (right thighs) based on a cellulite graded severity chart. During the second stage, the same photographs were examined by paired evaluators who had received additional training. Scores were independently moderated by a third person. The inter-rater reliability and intra-rater reliability over a 4-week interval were evaluated using intraclass correlation coefficients (ICCs). RESULTS: Twenty-four female participants (18-51 years, mean 31.68 ± 9.03 years) with a mean BMI of 29.04 ± 6.52 participated in the trial. Five female evaluators completed the initial evaluations. In stage 1, the inter-rater reliability (ICC2,5 ) was 0.838 (95%CI:0.700-0.922) and test/retest ICC3,1 values ranged from 0.360-0.990. In stage 2, the inter-rater reliability for 2 evaluators improved to 0.978 (95%CI:0.948-0.991), and the test/retest reliability of the moderated scoring method improved to 0.993 (95%CI:0.983-0.997). CONCLUSION: The iterative process developed a simple and reliable method of rating cellulite severity, with excellent inter-and intra-rater reliability, based on evaluating images of cellulite against a standard set of graded severity images. A reliable method of assessing cellulite severity is essential for undertaking future clinical trials to evaluate cellulite treatments.

Comparison of physical enhancement technologies in the skin permeation of methyl amino levulinic acid (mALA).

Physical drug delivery enhancement in skin has been shown to enhance cosmeceutical actives efficacy. Among the physical drug delivery enhancement technologies, microneedle is the most commercially successful technology. However, there are pros and cons like other physical enhancement technologies including variabilities in penetration depth and lack of efficacy. In this study, three physical topical dug delivery enhancements, elongated microparticles, microneedles and dermaroller, were applied to ex vivo pig skin and compared. The model topical drug that was used is 5-Aminolevulinic acid, the most commonly used photosensitiser prodrug. The skin was pre-treated before mounting on to Franz cell diffusion apparatus. Transdermal epidermal water loss was measured, and receptor fluids were collected at 7 time points for HPLC analysis. The results show that all three technologies disrupted the skin surface. All microporation pre-treatments significantly enhanced mALA cumulative permeation over 8 h (p < 0.001), with the 24x dermaroller significantly greater than 12x dermaroller (p < 0.001) and both dermaroller treatments significantly greater than microneedles and elongated microparticles (p < 0.05). The microporation pre-treatments all significantly increased mALA deposition in the stratum corneum and deeper skin tissues compared to passive administration, with deposition increases ranging from 3.6x to 15.1x that of passive administration. The DR pretreatment showed highest enhancement ratios (amount 5-Aminolevulinic acid in skin at 8 h following pretreatment v passive) with the following order of enhancement: 24x dermaroller > 12x dermaroller > microneedles > elongated microparticles. In conclusion, physical enhancement tools such as microneedles, dermarollers and elongated microparticles demonstrated significant penetration and retention of mALA through/into piglet skin. Further study is needed to determine the cost, dose and patient compliance.

Novel Self-Nano-Emulsifying Drug Delivery Systems Containing Astaxanthin for Topical Skin Delivery.

Astaxanthin (ASX) is a potent lipophilic antioxidant derived from the natural pigment that gives marine animals their distinctive red-orange colour and confers protection from ultraviolet radiation. Self nano-emulsifying drug delivery systems (SNEDDS) have been successfully developed and evaluated to increase the skin penetration of ASX and target its antioxidant and anti-inflammatory potential to the epidermis and dermis. SNEDDS were prepared using a low-temperature spontaneous emulsification method, and their physical characteristics, stability, antioxidant activity, and skin penetration were characterized. Terpenes (D-limonene, geraniol, and farnesol) were included in the SNEDDS formulations to evaluate their potential skin penetration enhancement. An HPLC assay was developed that allowed ASX recovery from skin tissues and quantification. All SNEDDS formulations had droplets in the 20 nm range, with low polydispersity. ASX stability over 28 days storage in light and dark conditions was improved and antioxidant activity was high. SNEDDS-L1 (no terpene) gave significantly increased ASX penetration to the stratum corneum (SC) and the epidermis-dermis-follicle region (E + D + F) compared to an ASX in oil solution and a commercial ASX facial serum product. The SNEDDS-containing D-limonene gave the highest ASX permeation enhancement, with 3.34- and 3.79-fold the amount in the SC and E + D + F, respectively, compared to a similar applied dose of ASX in oil. We concluded that SNEDDS provide an effective formulation strategy for enhanced skin penetration of a highly lipophilic molecule, and when applied to ASX, have the potential to provide topical formulations for UV protection, anti-aging, and inflammatory conditions of the skin.

Novel Nanocarriers for Targeted Topical Skin Delivery of the Antioxidant Resveratrol.

Resveratrol (RSV) is a potent lipophilic antioxidant with a low aqueous solubility. Novel nanoformulations have been successfully developed and evaluated to increase the potential of resveratrol as a skin targeting antioxidant. Nanoformulations were prepared using a spontaneous emulsification method, and characterized and evaluated for their capabilities to penetrate/permeate the skin. In nanoformulations, the thermodynamic activity of the RSV penetration into/permeation through the skin was correlated with the thermodynamic activity of the RSV in the formulations. When terpenes were incorporated into the nanoformulations, the permeation of RSV through the skin increased and correlated with an increasing lipophilicity of the terpene. The nanoemulsion containing eugenol showed the highest RSV penetration into the stratum corneum (SC) and the epidermis-dermis-follicle region, whereas the limonene containing nanoemulsion had the highest RSV permeation through the skin (the enhancement ratios, compared to a saturated solution of RSV, were (i) 9.55 and (ii) 12.61, respectively, based on the average RSV amount (i) in each skin region and (ii) permeation through skin).

Topical Nano and Microemulsions for Skin Delivery.

Nanosystems such as microemulsions (ME) and nanoemulsions (NE) offer considerable opportunities for targeted drug delivery to and via the skin. ME and NE are stable colloidal systems composed of oil and water, stabilised by a mixture of surfactants and cosurfactants, that have received particular interest as topical skin delivery systems. There is considerable scope to manipulate the formulation components and characteristics to achieve optimal bioavailability and minimal skin irritancy. This includes the incorporation of established chemical penetration enhancers to fluidize the stratum corneum lipid bilayers, thus reducing the primary skin barrier and increasing permeation. This review discusses nanosystems with utility in skin delivery and focuses on the composition and characterization of ME and NE for topical and transdermal delivery. The mechanism of skin delivery across the stratum corneum and via hair follicles is reviewed with particular focus on the influence of formulation.