Microneedle Patches Coloaded with 4-MSK and <i>C. Reinhardtii</i> Alleviate Melanin Deposition Through Multipathway Synergy

Hyperpigmentation (HP) is mainly triggered by ultraviolet irradiation or local inflammation, and the free radicals generated by these two factors are the core inducers of various skin diseases. This study proposes a multipathway and highly efficient treatment strategy for melanin deposition. A microneedle (MN) system based on hydrolyzed collagen (HC) and polyvinylpyrrolidone (PVP) was designed to precisely deliver <i>Chlamydomonas reinhardtii</i> (<i>C. reinhardtii</i>) and potassium 4-MSK (C.r&4-MSK-MN) to skin tissues. <i>C. reinhardtii</i> contains unique antioxidant components such as arsenoproteins, polyunsaturated fatty acids (PUFAs), and algal polysaccharides, which distinguish it from other microalgae like <i>Chlorella</i>. <i>In vitro</i> free radical scavenging experiments show that at a concentration of 1 × 10⁹ cells/mL, <i>C. reinhardtii</i> exhibits scavenging rates of 89.26%, 101.44%, and 103.57% against DPPH·, ABTS·⁺, and ·OH radicals, respectively. In addition, potassium 4-methoxysalicylate (4-MSK) can inhibit tyrosinase activity and promote skin metabolism. Therefore, C.r&4-MSK-MN has the following advantages: on one hand, C.r&4-MSK-MN successfully breaks through the skin barrier, directly delivering <i>C. reinhardtii</i> cells to the target site to scavenge free radicals and reduce the stimuli for melanin production. On the other hand, 4-MSK inhibits tyrosinase activity to reduce melanin synthesis and, at the same time, promotes skin metabolism to reduce melanin deposition on the skin surface, achieving multipathway reduction of melanin deposition. Experimental results showed that in animal models, C.r&4-MSK-MN significantly reduces the epidermal thickness of rats and substantially decreases melanin production. This research outcome not only provides a new strategy for the treatment of melanin deposition but also confirms that microalgae have potential application prospects in the fields of skin care (such as whitening and antiaging) and cosmeceuticals.