**3. Discussion**

Liposomes in themselves are relatively unstable delivery systems because of their membrane instability in aqueous solution, which can affect their bioavailability and pharmacological effect, the addition of adjuvants being necessary to bring more rigidity and stability. AST seems to enhance the liposomes' stability when on the membrane, which helps its delivery. The strategy of adding other adjuvants to improve membrane rigidity seems to be necessary to ensure stability, which should be taken into account when assessing production costs. Reducing the particle size with the development of nanoliposomes seems to be an excellent alternative method to improve their stability and consequently their penetration, solubility, and continuous release; however, it is still necessary to consider the machinery and costs involved. Another innovative alternative method to deliver AST on deep skin layers is the use of the iontophoretic technique with charged delivery systems, developed with liposomes, which makes it possible to reach the stratum corneum and act as a whitening agent.

Emulsion delivery systems, especially nanoemulsions, are an effective and widely applied form to deliver bioactive compounds in medicines and cosmetics. Due to the hydrophobic character of AST, most of the nanoemulsions prepared in the literature are

oil/water systems. Studies based on experimental design allow researchers to identify the best conditions for nanoemulsion preparation, with reduced time and costs of research. In addition, nanoemulsions can be incorporated in other delivery systems, such as films, which can significantly improve their biological effects and their acceptance by the patient or customer. Unfortunately, only one article was found concerning the use of microemulsions in dermatological and cosmetics applications. More investment in research on this new product delivery system is desirable.

Particulate systems are a promising alternative way to develop innovative formulations for AST delivery, thanks to the possibility of using different matrix components and methods to form spheres and capsules at micro- or nanoscale. Similar to nanoemulsions, studies based on experimental design can be performed to optimize the conditions needed to prepare particulate systems. It is important to consider alternative methods, to prevent AST degradation. Some articles on particulate systems considered in this review presented either ecological or natural alternatives to develop delivery systems, which can aggregate to more sustainable products.

The use of CDs as systems to gues<sup>t</sup> AST in inclusion complexes is able to significantly improve the solubility of hydrophobic compounds like AST. However, it would be necessary to have a greater number of inclusion complexes, in order to carry out a comparison by which to identify the most advantageous system. From the results examined in this review, it is possible to state that AST can form inclusion complexes either with natural CDs, such as β-CDs, or with modified CDs, such as hydroxypropyl β-CD. Films for the delivery of bioactive compounds on the skin are an alternative, especially for wound healing and scald treatments. The antioxidant effect accelerates the healing process, due to its antiinflammatory activity. The AST-incorporating films may also be applied as an easy adjunct treatment, to treat skin cancer, which should be considered in the research. In addition, AST seems to act merely as an active principle, which requires a film-forming agen<sup>t</sup> such as collagen, chitosan, cellulose derivatives, and others to create the film structure.

The systems that seem to be more developed and robust are the emulsions and the particulate systems, given the large number of articles and assays performed on them. However, they are not the only systems to consider. On the other hand, the limited studies carried out on other systems, many of which are not mentioned in this review article, show opportunities for the development of new and innovative formulations. Examples are solid dispersions, transdermal systems, and others.
