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

that exists in a liquid state with fl owability and low viscosity at low temperatures (less than 4°C) and forms a gel at elevated temperatures (body temperature) (16). PLO gel is physical organogel that is typically formulated by undergoing the heating–cooling process. These organogels consist of lecithin-based phospholipids and polymeric surfactant molecules by forming a three-dimensional network of polymers. Because PLO gel was formed by adding droplets of water into a system, this type of matrix can be formulated as a reverse micellar–based organogel system by combining hydrophilic linkers (17). Lecithin is a mixture of phospholipids containing phosphatidylcholine and a naturally occurring biocompatible substance that can form diverse types of supramolecular struc- tures in collaboration with water (18,19). In the preparation of PLO gel, lecithin assem- bles into reversed polymer-like micelles when water is added, and initial micelles gradually tangle together into a three-dimensional network in the bulk phase when added to oil by dissolving trace amounts of water. This study was performed to develop PLO gel into cosmetic formulations as PLO gel has drawn much attention as a TDDS. In the previous literature, the poloxamer 407 solution at a certain concentration had liquidity at room temperature or below, and micelles turned into PLO gel at body tem- perature in the formation of ordered cuboidal structures due to the dehydration of the micellar core at elevated temperature (20). This process has the advantage of cost- effectiveness by effi ciently concentrating a specifi c drug at the right time and place and increasing drug safety (8). However, this also presents a limitation to be used in cosmetics that requires cosmetic shelf life and stability at low temperature. To improve the fl owability and phase separation of PLO gel at low temperatures to be applied in cosmetic formulations, this study intends to propose PLO gel formulation suitable for cosmetics through the measurement of time-elapsed change at different tem- peratures, fi eld emission scanning electron microscope (FE-SEM), differential scanning calorimetry (DSC), rheology, and skin permeation effi ciency using the response surface methodology (RSM). MATERIALS AND METHODS MATERIALS In the preparation of PLO gel, poloxamer 407 (Pluronic F127 NF, BASF, Ludwigshafen, Germany), cetyl ethylhexanoate (CEH, Kokyu Alcohol Kogyo Co., Chiba, Japan), PEG- 400 (SFC Co., Ltd., Seoul, Korea), 1,2-hexanediol (Twinchem Inc., Gwangju, Korea), butylene glycol (1,3-butylene glycol, Daicel, Hiroshima, Japan), dipropylene glycol (Dipropylene glycol care, BASF), pentylene glycol (Hydrolite-5, Symrise, Holzminden, Germany), phenoxyethanol (Phenoxyethanol, Galaxy, Mumbai, India), and hydrogenated lecithin containing 75% phosphatidylcholine were used in the present study. In general, purifi ed water (DI-water) used in cosmetics was prepared using a water distillation apparatus (pure RO 130, Human Co., Seoul, Korea). To assess skin permeation effi ciency, niacinamide (Western Drug, Mumbai, India) was used as an indicator substance. For mixing, agi-mixer (overhead stirrer, SL4000, Global Lab, Siheung, Korea) and a hot plate (hot plate stirrer, HS-20, LK Lab Korea, Namyangju, Korea) PREPARATION AND EVALUATION OF PLURONIC LECITHIN ORGANOGELS 327