The tripeptide copper complex, glycyl-L-histidyl-L-lysine-Cu²⁺ (GHK-Cu), has a long history of safe use in cosmetic products and exhibits exceptional regenerative and anti-inflammatory properties [1]. These properties make it a valuable ingredient in modern cosmetic formulations that support skin renewal. However, its limited skin permeability and relatively high price pose some barriers to widespread use. The encapsulation of GKH-Cu in liposomes offers a potential solution as they can efficiently penetrate the epidermal barrier due to their epidermal-like lipid composition and provide a sustained release of the active ingredient [2]. Prolonged release and continuous absorption over time increase the benefits between applications of the topical formulation. As a result, fewer active ingredients are needed to achieve better results, significantly reducing the cost of the cosmeceutical product.

Here, we describe the formation of liposomes with GHK-Cu using a simple ethanol injection method that can be easily applied on an industrial scale. Capillary electrophoresis hyphened with inductively coupled plasma tandem mass spectrometry is used to confirm vesicle formation and GHK-Cu encapsulation. The amount of free and encapsulated metal complex in crude suspensions is determined based on signals obtained for copper (⁶³Cu⁺, m/z = 63, GHK-Cu marker) and phosphorus (³¹P¹⁶O⁺, m/z = 47, liposome marker) using the optimized CE-ICP-MS/MS method. The influence of the lipid composition on the encapsulation efficiency is examined. Moreover, different approaches of liposome post-formation treatments are also explored, aiming at enhanced complex loading. We found that the liposomes with a size below 200 nm of various compositions are stable for at least two weeks and emerge as promising biocompatible delivery systems that could enhance the therapeutic effect of the anti-aging metal complex and promote its use in cosmeceutical formulations.