Preparation and Physicochemical Properties of a Cysteine Derivative‐Loaded Deformable Liposomes in Hydrogel for Enhancing Whitening Effects

Abstract

Whitening materials cannot easily cross the skin barrier (stratum corneum) to reach melanocytes in the basal layer for inhibiting melanin production. This study aims to construct a novel deformable liposome using polyglyceryl‐3‐methylglucose distearate as an edge activator and a hydrogel containing hyaluronic acid (HA) and hydroxyethyl cellulose (HEC), as well as to investigate the synergistic effect of this system on the delivery of a cysteine derivative, methyl‐2‐acetylamino‐3‐(4‐hydroxyl‐3,5‐dimethoxybenzoylthio)propanoate (MP) as a whitening agent. The optimized deformable liposome (DL2) contains 10% edge activator and has a particle size of 78.2 ± 2.7 nm, a zeta potential of −29.9 ± 1.8 mV, a polydispersity index of 0.248, and an entrapment efficiency of 90.7 ± 1.7%. MP‐loaded DL2 has higher stability and deformability than DL2 without MP, as well as exerting a higher whitening effect than that observe with MP alone. In addition, MP‐loaded DL2 is incorporated into a hydrogel in a dual drug‐delivery system and the stability after hydrogel incorporation is evaluated. In Franz cells, the MP‐loaded deformable liposome‐hydrogel complex shows the highest skin permeation and penetration of MP. Practical Applications: In general, it is very difficult for whitening agents to penetrate a skin layer for reducing skin pigmentation. It is important to transfer whitening agents to the basal layer without causing physical damage to the skin. Deformable liposomes containing 10% polyglyceryl‐3‐methylglucose distearate in a hydrogel complex maximize the skin permeation of a cysteine derivative as a whitening agent. This finding indicates that the deformable liposome‐hydrogel complex is a potential delivery system for treatment of skin hyperpigmentation. The penetration mechanism of drugs in the skin by deformable liposome‐hydrogel complexes is as follows: Hydrogel hydrates stratum corneum to secure the route of drugs or nanocarrier permeation. polyglyceryl‐3‐methylglucose distearate as an edge activator enhances the fluidity of the stratum corneum lipid layer and the deformability of liposome. The edge activator‐based deformable liposomes pass through the stratum corneum stably.

Nanosystems with potential application as carriers for skin depigmenting actives

“…Liposomes were obtained with an average size of 78.2 ± 2.7 nm and encapsulation efficiency of 90.7 ± 1.7%. Through tests on B16F1 melanoma cells, it was verified that deformable liposomes improved the whitening efficacy due to their ability to fuse with cell lipid membranes, in addition to increasing the penetration capacity of the assets and their accumulation in deeper layers of the skin [60]. Lee et al also studied liposomes with penetration-inducing agents, ceramide and fatty acids, for the encapsulation of the active niacinamide and adenosine, as a proposal for a depigmenting formulation that reduces the signs of aging.…”

Liposome Deformation Induced by Membrane-Binding Peptides

“…The control of liposome shape has been a topic of investigation in molecular robotics, as deformability is a necessary characteristic for movement within micro and crowded environments, such as within living organisms or soil. For example, deformable liposomes containing surfactants have been shown to permeate human skin, enabling the transdermal transport of drugs [ 8 , 9 ]. Several approaches have been proposed to deform liposomes, including the use of surfactants [ 10 , 11 ], proteins [ 3 , 12 , 13 ], and peptides [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Selected Physicochemical Properties of Lyophilized Hydrogel with Liposomal Fraction of Calcium Dobesilate

“…Methylcellulose in aqueous conditions may represents thermoreversible semi-solid hydrogel, applicable for food, pharmaceutical, cosmetic, textile, and biomedical industries [11]. Liposomal hydrogels are intensively developed for controlled drug delivery via oral [12] and nasal mucous [13], as well as dermatological preparations [14].…”