ObjectiveThe permeation of hydrophilic molecules through the skin is still a challenge due to the barrier posed by stratum corneum, the outermost layer of the skin. Liposomes have frequently been used as carriers for different types of drugs and may also function as permeation enhancers. Propylene glycol has also been used as an edge activator in liposomes to increase the permeation. The aim of this work was to prepare liposomes containing an edge activator and loaded with caffeine to evaluate the potential of caffeine reaching the deeper layers in the skin.MethodsThe formulations were prepared by a top‐down process using high‐pressure homogenization at 200 00 psi for 10 min. They were characterized by size, polydispersity index (PI), zeta potential (ZP), pH, caffeine content and encapsulation efficiency (EE%) on preparation (time zero) and after 30 days. Cytotoxicity of blank and loaded liposomes was assessed by MTT proliferation assay with a normal keratinocyte cell line (HaCaT). In vitro permeation tests were performed with human skin in Franz cells over 24 h, and caffeine concentration was determined in the skin surface, stratum corneum, dermo‐epidermal fraction and receptor medium by HPLC.ResultsThe caffeine liposomes with (DL‐Caf) or without propylene glycol (CL‐Caf) showed, respectively, mean size 94.5 and 95.4 nm, PI 0.48 and 0.42, ZP + 1.3 and + 18.1 mV and caffeine content of 78.57 and 80.13%. IC50 values of caffeine in DL‐Caf (3.59 v/v %) and CL‐Caf (3.65 v/v %) were not significantly different from conventional blank liposome (3.27 v/v %). The DL‐Caf formulation presented the best capability to enhance the caffeine permeation through the skin, resulting 1.94‐folds higher than caffeine solution. Furthermore, the caffeine flux from DL‐Caf was 1.56‐ and 3.05‐folds higher than caffeine solution and CL‐Caf, respectively. On the other hand, CL‐Caf showed the lowest caffeine penetration revealing the importance of edge activator to aid hydrophilic drug penetration to all skin layers.ConclusionThe DL‐Caf formulation tested was able to improve the permeation of caffeine through the stratum corneum and dermo‐epidermal layers, suggesting that this delivery system may be effective for deep skin delivery of hydrophilic drugs.

A range of liquid emollient ester-loaded body emulsions were evaluated on the basis of sensory profile, consumer perception, physicochemical, biometrological, and rheological performances. This was complemented by skin hydration and transepidermal water loss (TEWL) studies performed using a Corneometer ® and Tewameter ® , respectively. The rheological studies showed similar behavior of creams on variation of shear stress, frequency, and temperature. However, skin hydration performances of creams were found varied when compared between base cream and emollient ester-containing creams. In case of the TEWL study, base cream (F1, no ester) and octyl palmitate-containing cream (F2), exhibited the most protective behavior for the skin with minimal water loss. Sensory profiles of creams were obtained using the sensory descriptive analysis method. A study performed with human consumers (as subjects) using the difference of test attributes (directional) method showed the importance of sensory evaluation with consumers and proved to be an interesting analysis for comparison with the sensorial profile. In this case, the attributes with the highest intensity in the evaluated creams were, that is, spreadability, slipping, and dry touch. Stability studies of creams were performed for 90 days under different storage conditions. Stability studies showed octyl stearate-containing (F2) and palmitate-containing (F5) creams exhibited best stability under extended storage conditions. This research has demonstrated the importance of physicochemical characterization and sensory evaluations performed with consumers for more targeted analysis of cream-based formulations to differentiate product characteristics and identify attributes-led preferences. Practical applicationsResults from the present work suggest that emollients are directly responsible for sensory characteristics such as spreading, absorption, and touch on the skin; they can influence the viscosity and appearance of emulsions. After application on the skin, they regulate the moisture content of the epidermis together with the humectants. This research has demonstrated the importance of sensory evaluation, especially performed with consumers, which may be considered a more targeted analysis to differentiate product characteristics and help in the choice of emollient with the desired characteristics for the cosmetic product.

Mosquito-borne diseases affect millions of people worldwide each year, and the use of a topically applied insect repellent is an economically viable preventative health practice. The general objective of this work was to encapsulate citronella oil (CO) in a nanostructured lipid carrier (NLC) to formulate a topical repellent with a long duration of efficacy on the skin and a good safety profile based on minimizing skin penetration. In the studied CO, the main chemical constituents of geraniol, citronellal, and citronellol were identified and subsequently used as markers for the in vitro skin permeation testing (IVPT). An optimal NLC encapsulating CO formulation was developed and had an average particle size of 350 nm. The NLC was then formulated in combination with CO at ratios of 2:1, 1:1, and 1:2 CO:NLC-CO as oil-in-water (O/W) emulsions and compared to CO in the same O/W emulsion base (all at 10% CO in the final O/W topical formulation). The markers geraniol, citronellol, and citronellal were detected in all samples tested F1 (10% CO in O/W emulsion) and F3 (10% CO/NLC-CO 1:1 in O/W emulsion). Even the percentages of F3 markers were higher than F1. The recovery of the percentage balance (based on the total remaining on the skin surface, on the skin, and penetrated through the skin to the receptor) of geraniol, citronellol, and citronellal markers for F1 and F3 was 7.70% and 11.96%; 25.51% and 31.89%; and 5.09% and 4.40%, respectively. The nanoparticle lipid solid forms a repellent reservoir on the skin surface, releasing the active ingredients slowly through volatilization, extending the repellent action, and reducing permeation through the skin. It is possible to assume that the remaining 92.30% and 88.03%; 74.49% and 68.11%; and 94.10% and 95.60% of geraniol, citronellol, and citronellal markers of F1 and F3, respectively, were lost to evaporation. In the in vivo efficacy test carried out with the Aedes aegypti mosquito, F3 was the optimal formulation, providing the greatest repellent action compared to free oil in O/W emulsion. Thermal analysis showed that the NLC-CO raised the boiling point of the encapsulated CO compared to the free oil, suggesting that the controlled release of the CO was a possible mechanism for its prolonged effect. We concluded that the nanocarriers developed with CO were stable and provided improved mosquito-repellent efficacy with minimal skin penetration of the CO actives over 24 h. Indeed, regardless of whether the CO was applied as free oil, a 1:1 mixture of CO (pure/free oil) or NLC-CO applied in an O/W emulsion can be considered safe for topical application due to minimal skin penetration.