Engineering of New UV-Blocking Hollow Proteinoid Nanoparticles of Narrow Size Distribution Containing All-trans Retinoic Acid for Biomedical Applications

All-trans retinoic acid (at-RA), the most active form of vitamin A, is known to be highly beneficial in dermatology.
At-RA can reduce acne vulgaris symptoms and improve the skin appearance significantly. Moreover, at-RA is a useful
treatment for different skin diseases and for several types of cancer. However, it is extremely sensitive when exposed
to ultraviolet (UV) light, due to conjugated double bonds that comprise its chemical structure. In order to increase
the benefits of topical use of at-RA, a new drug carrier encapsulating and protecting at-RA from light-dependent
degradation, is designed and presented here. Proteinoids are biocompatible polymers made from amino acids by
thermal step-growth polymerization. These polymers form hollow nanoparticles in an aqueous solution by a simple selfassembly process, during which suitable molecules may be encapsulated within the particles. Thus, newly designed
UV-absorbing proteinoids were utilized to encapsulate at-RA acid. New proteinoids were synthesized by thermal stepgrowth polymerization of glutamic acid, phenyl alanine and tyrosine in absence or presence of the UV absorber paraaminobenzoic acid. The proteinoids were of relatively high molecular weights and narrow molecular weight distributions
(42-84 kDa, PDIs of 1.02-1.12). At-RA, was then successfully encapsulated (up to 20%) within the self-assembled
proteinoid nanoparticles dispersed in an aqueous continuous phase. The proteinoid nanoparticles were able to protect
the at-RA from light dependent degradation up to 94% over 24 h, while under similar conditions free at-RA degraded
entirely over 3 h. The study also indicates that both the hollow and retinoic acid-filled particles are non-toxic and cellpermeable in HaCaT cells, a human epithelial cell line. The study suggests that at-RA-filled proteinoid nanoparticles
protect at-RA from light-dependent degradation, offering significant advantage over free at-RA. Therefore, the optimal
proteinoid particles chosen may potentially be used for acne vulgaris treatment as well as other biomedical applications
requiring UV-protected retinoic acid.