Preparation and Evaluation of Pluronic Lecithin Organogels in Cosmetics SEONG JUN YANG and KYUNG-SUP YOON , Department of Chemistry & Cosmetics, Jeju National University, Jeju-do 63243, Korea (S.J.Y, K.-S.Y.) Accepted for publication March 1, 2021. Synopsis This study was performed to investigate the application of pluronic lecithin organogel (PLO gel) in cosmetics as a topical drug delivery system. PLO gel was known as transdermal drug delivery systems. It has a very interesting system, owing to their biocompatibility their amphiphilic nature, facilitating dissolution of various drug classes and their permeation enhancement properties. We realized that PLO gel has a critical shortcoming of fl owability at low temperatures to be used as a cosmetic ingredient. To improve this drawback, this study aimed to fi nd an appropriate quantity of three main compositions of PLO gel, including aqueous phase (poloxamer 407 and water), polyol phase (PEG-400), and oil phase (lecithin and oil), and applied an experimental design using the response surface methodology (RSM). We assessed the elapsed time change by temperature in each PLO gel formulation, observed the morphology of PLO gel using fi eld emission scanning electron microscope (FE-SEM), and determined the gelation point by using differential scanning calorimetry (DSC). Rheology measurements to assess viscoelastic properties were determined by using a rheometer, and skin permeation effi ciency was assessed by diffusion system. It was confi rmed that three main factors (hydrogenated lecithin, PEG-400, and poloxamer 407) of PLO gel should be balanced without fl owability even in cold temperature. Through the RSM, it was assumed that the most effective ingredient was PEG-400 at PLO gel formulation and physical properties. The PLO gel formulation (hydrogenated lecithin 5.0%, PEG-400 20.0%, and poloxamer 407 15.0%) was evaluated as the most suitable formulation for use in cosmetics due to its viscosity and elasticity results. The shape was observed through FE-SEM, and it was confi rmed that the PLO gel forms a polymeric bicontinuous microemulsion structure. Regarding the applicability of PLO gel in cosmetics, we verifi ed that PLO gel can be used in a delivery system for active substances. The study fi ndings suggest that PLO gel can be used as one of the ingredients in cosmetic formulations. INTRODUCTION Topical and transdermal drug delivery systems (TDDSs) are widely used in the fi eld of drug delivery systems (DDSs). These DDSs are most commonly designed to deliver the drugs through the skin. The skin is composed of three main layers: the epidermis, the dermis, and the subcutaneous fat tissue (1). A variety of advanced DDSs has been formu- lated to facilitate drug delivery through the epidermis and dermis, but do not allow suc- cessful drug deliver via the epidermis layer. The special characteristic of TDDSs is to Address all correspondence to Kyung-Sup Yoon at ksyoonjh@jejunu.ac.kr. J. Cosmet. Sci., 72, 325–346 (May/June 2021) 325

achieve the balance to deliver hydrophilic and hydrophobic drugs through the epidermis (2). The stratum corneum is the major barrier in drug permeation across the skin. To overcome the limitation, chemical penetration enhancers (CPEs) are commonly used in TDDSs. However, CPEs could destroy the fat layer of the skin, and its long-term use may cause irritation and sensitivity to the skin (3–5). TDDSs responsible for the transport of drugs through the skin have gained much atten- tion and have been continuously studied in the pharmaceutical and cosmetic industries because these systems can maintain consistent drug plasma concentration and immedi- ately provide the desired therapeutic effi cacy by not being metabolized in the liver or the stomach. Because skin as a delivery route for drugs has increasingly attracted a great at- tention from many researchers, TDDSs have emerged as an attractive alternative for oral delivery of drugs as the reduction of gastrointestinal problems by drug delivery through the skin has been reported (6). Poloxamer 407 and lecithin are most commonly used substances in topical delivery of drugs. Most of the studies have demonstrated that pluronic lecithin organogel (PLO) gel has the unique capacity to transport drugs across the skin. Drug permeability of PLO gel has been improved by lecithin and organic solvent used for its preparation. Lecithin in- creases drug permeation by temporarily opening skin pores and making epidermal struc- tures more fl exible (2,7). Through this process, lecithin enables topical drug delivery through the skin without skin irritation. Topical drug treatment aims at providing high concentration of drugs at the desired site to avoid systemic side effects associated with oral administration of drugs. To facilitate transdermal drug delivery after topical applica- tion, these agents are formulated in a matrix type (8). PLO gel is a soya lecithin–based yellow-colored, odorless, and nontransparent gel that is characterized by rapid absorption. Because of the unique physical nature, it is commonly used as a drug delivery vehicle including poloxamer 407, a viscosity-enhancing agent with surfactant properties that facilitate oil-in-water preparations. Other common ingre- dients of PLO gel include lecithin, isopropyl palmitate, isopropyl myristate, polyethylene glycol, sorbic acid, and potassium sorbate (9). PLO gel is a very interesting TDDS characterized by unique properties including bio- compatibility, amphiphilic nature, dissolution of various active substances, and perme- ation enhancement (10). PLO gel was fi rst developed as a topical drug vehicle by an American pharmacist in the early 1990s and is currently of a great attention in the pharmaceutical sector. Sudaxshina Murdan, a pharmacist, suggests, “Based on the greater aqueous component of the gel one could say that PLO gel is a hydrogel” (11). The hydrogel system, a three-dimensional network of hydrophilic polymers, is capable of absorbing large quantities of water or biological fl uids. Atrophic homopolymers or copolymers form an atrophic network via cross-bridge binding. Physical crosslinking includes molecular entanglement or crystallization that contributes to the formation and physical integrity of the network, and chemical crosslinking can be considered as the binding point and bonding (12–14). Because hydrogels are easily washed away, but adhere well to the mucosa or the skin by existing in wet forms due to cellular fl uid, the hydrogel system is generally applied to damaged skin and eyes (15). PLO gel is mainly made up of two phases, aqueous phase (poloxamer 407) and oil phase (lecithin). Polox- amer 407 is an ABA-type triblock copolymer composed of 70% polyoxyethylene with the average molecular weight of 12,500 Da (10). Poloxamer 407 is a nontoxic polymer JOURNAL OF COSMETIC SCIENCE 326