A kind of salicylic acid nanoemulsion with sustained and controlled release effect and research on its anti-acne efficacy
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Presented by: Wangwang Lu
Background
In some researches indicate that salicylic acid can be used to remove acne, which mainly depended on its ability to penetrate into pores through sebaceous glands to dissolve sebum, peel off horniness, remove blackheads and improve clogged pores. Besides, salicylic acid has antibacterial and bactericidal effects on Propionibacterium acnes, Staphylococcus aureus, etc., which may cause inflammation of hair follicles, skin suppuration or infection，and also can effectively improve and treat acne. However, the solubility of salicylic acid is extremely low, so that it is difficult to applied to the formulation. In addition, high concentrations of salicylic acid are very irritating to skin.Therefore, in order to overcome the shortcomings of free salicylic acid and improve its bioavailability, it is urgent to explore and develop a stable and low irritating salicylic acid transport carrier, so that it can effectively achieve skin anti-acne effects.
Objective
The purpose of this research was to develop a salicylic acid nanoemulsion in order to effectively achieve anti-acne effects without irritation.
Methods
Salicylic acid nanoemulsion was prepared by ultra-high pressure homogenization. The particle size and PDI of nanoemulsion were determined by dynamic light scattering, and the encapsulation efficiency and loading capacity of salicylic acid nanoemulsion were evaluated by an ultrafiltration method. The safety of 2% salicylic acid nanoemulsion was determined by the patch test of 21 people. The sustained and controlled release behavior of salicylic acid nanoemulsion was studyed by the dialysis bag method in which the controlled release behavior was further explored by adding lipase. The antibacterial effect of salicylic acid nanoemulsion solution against Propionibacterium acnes was evaluated by agar plate diffusion method (perforation method). The skin anti-acne effect was assessed by clinical trial, in which 33 volunteers aged 18-35, including 3 males and 30 females, respectively, with mild to moderate facial acne, were recruited to use a gel mask (containing 6.4% salicylic acid nanoemulsion, namely 2% free salicylic acid) every night, staying for 30 minutes, and then wash it with warm water, and gel mask was continuously uesd for a period of 4 weeks. Then, self-randomized parallel control clinical evaluation method was used to evaluate the improvement of acne after using the product.
Results
The results showed that the particle size, PDI of salicylic acid nanoemulsion were 21.4 nm, 0.107, respectively.The encapsulation efficiency was 83.7%, and the loading capacity was 30.0%. Human patch test showed that 21 subjects did not have any adverse reaction, which indicated that 2% salicylic acid nanoemulsion prepared in this test was not irritating to human skin. Besides, vitro sustained-release experiments showed that the release time of salicylic acid nanoemulsion was 5 times longer than that of free salicylic acid, and vitro controlled release experiments showed that, the release time of salicylic acid increased from 19% to 52% for 2 hours in the presence of lipase, which obviously accelerated the release of salicylic acid. It could be seen that salicylic acid nanoemulsion had the characteristics of sustained and controlled release. Besides, by agar plate diffusion method, the experiment showed that the average size of bacteriostatic circle of free salicylic acid and salicylic acid nanoemulsion were 7.23 mm and 9.49 mm, respectively, which indicated that the bacteriostatic effect of salicylic acid was significantly improved after nano-encapsulation. During a 28-day clinical trial, there was no grade 1 or above skin adverse reaction after using the product, which proved that the product had good safety. In addition, this product had a significant acne removing effect, in which, the number of non-inflammatory acne (blackheads and whiteheads) decreased 30.04%, and the number of inflammatory acne (red papules and pustules) decreased 20.71%.
Conclusion
Salicylic acid nanoemulsion prepared in this study contained triglyceride, and in acne and other inflammatory sites, lipase could degrade the matrix material of triglyceride nanocarrier, and trigger nanocarrier to decompose and release salicylic acid, and then realize controlled release of target site and enhance its antibacterial effect. Secondly, the anti-acne efficacy and safety of the salicylic acid nanoemulsion had been effectively proved in clinical trial. To sum up, nano-emulsification technology could achieve targeted aggregation, controlled release, irritation reduction and synergism enhancement effects for skin anti-acne treatment, and provided new insight into the topical application of skin care cosmetics, especially skin anti-acne products.
In some researches indicate that salicylic acid can be used to remove acne, which mainly depended on its ability to penetrate into pores through sebaceous glands to dissolve sebum, peel off horniness, remove blackheads and improve clogged pores. Besides, salicylic acid has antibacterial and bactericidal effects on Propionibacterium acnes, Staphylococcus aureus, etc., which may cause inflammation of hair follicles, skin suppuration or infection，and also can effectively improve and treat acne. However, the solubility of salicylic acid is extremely low, so that it is difficult to applied to the formulation. In addition, high concentrations of salicylic acid are very irritating to skin.Therefore, in order to overcome the shortcomings of free salicylic acid and improve its bioavailability, it is urgent to explore and develop a stable and low irritating salicylic acid transport carrier, so that it can effectively achieve skin anti-acne effects.
Objective
The purpose of this research was to develop a salicylic acid nanoemulsion in order to effectively achieve anti-acne effects without irritation.
Methods
Salicylic acid nanoemulsion was prepared by ultra-high pressure homogenization. The particle size and PDI of nanoemulsion were determined by dynamic light scattering, and the encapsulation efficiency and loading capacity of salicylic acid nanoemulsion were evaluated by an ultrafiltration method. The safety of 2% salicylic acid nanoemulsion was determined by the patch test of 21 people. The sustained and controlled release behavior of salicylic acid nanoemulsion was studyed by the dialysis bag method in which the controlled release behavior was further explored by adding lipase. The antibacterial effect of salicylic acid nanoemulsion solution against Propionibacterium acnes was evaluated by agar plate diffusion method (perforation method). The skin anti-acne effect was assessed by clinical trial, in which 33 volunteers aged 18-35, including 3 males and 30 females, respectively, with mild to moderate facial acne, were recruited to use a gel mask (containing 6.4% salicylic acid nanoemulsion, namely 2% free salicylic acid) every night, staying for 30 minutes, and then wash it with warm water, and gel mask was continuously uesd for a period of 4 weeks. Then, self-randomized parallel control clinical evaluation method was used to evaluate the improvement of acne after using the product.
Results
The results showed that the particle size, PDI of salicylic acid nanoemulsion were 21.4 nm, 0.107, respectively.The encapsulation efficiency was 83.7%, and the loading capacity was 30.0%. Human patch test showed that 21 subjects did not have any adverse reaction, which indicated that 2% salicylic acid nanoemulsion prepared in this test was not irritating to human skin. Besides, vitro sustained-release experiments showed that the release time of salicylic acid nanoemulsion was 5 times longer than that of free salicylic acid, and vitro controlled release experiments showed that, the release time of salicylic acid increased from 19% to 52% for 2 hours in the presence of lipase, which obviously accelerated the release of salicylic acid. It could be seen that salicylic acid nanoemulsion had the characteristics of sustained and controlled release. Besides, by agar plate diffusion method, the experiment showed that the average size of bacteriostatic circle of free salicylic acid and salicylic acid nanoemulsion were 7.23 mm and 9.49 mm, respectively, which indicated that the bacteriostatic effect of salicylic acid was significantly improved after nano-encapsulation. During a 28-day clinical trial, there was no grade 1 or above skin adverse reaction after using the product, which proved that the product had good safety. In addition, this product had a significant acne removing effect, in which, the number of non-inflammatory acne (blackheads and whiteheads) decreased 30.04%, and the number of inflammatory acne (red papules and pustules) decreased 20.71%.
Conclusion
Salicylic acid nanoemulsion prepared in this study contained triglyceride, and in acne and other inflammatory sites, lipase could degrade the matrix material of triglyceride nanocarrier, and trigger nanocarrier to decompose and release salicylic acid, and then realize controlled release of target site and enhance its antibacterial effect. Secondly, the anti-acne efficacy and safety of the salicylic acid nanoemulsion had been effectively proved in clinical trial. To sum up, nano-emulsification technology could achieve targeted aggregation, controlled release, irritation reduction and synergism enhancement effects for skin anti-acne treatment, and provided new insight into the topical application of skin care cosmetics, especially skin anti-acne products.