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
were used. All ethyl alcohol (99.5%, Sigma-Aldrich, Darmstadt, Germany) and distilled water used in the assay were HPLC grade. METHOD OF PREPARATION PLO gel formed is liquid (a sol phase) at low temperatures (around 10°C) and undergoes a phase transition (a gel phase) when the temperature is elevated. Thermo-responsive polymers are macromolecular gels that undergo a sol–gel phase transition or volume phase transition depending on the outside temperature, and this reversible phase transi- tion can detect temperature change (21). A sol–gel phase transition is known to exhibit a reversible phase change as a system that physically forms hydrogels in response to tem- perature change (Figure 1A). Volume phase transition is the phenomenon of swelling– shrinking of gels depending on temperature change without being dissolved in water (Figure 1B). A critical solution temperature is the temperature at which a phase transi- tion occurs. Lower critical solution temperature (LCST) is the minimum temperature of phase transition in the concentration–temperature diagram and is the temperature at which phase separation occurs in the homogeneous phase with increasing temperature. Upper critical solution temperature (UCST) is the highest temperature at which an op- posite phase transition occurs (22,23). Since the UCST system has been limited by rela- tively high temperatures that could affect the properties of drugs or physiologically active substances, the LCST system has attracted much attention in drug delivery (24). There- fore, PLO gel exhibits the LCST behavior, and this is attributable to the unique charac- teristic of poloxamer 407 that shows fl owability at low temperatures. F or the preparation of the water phase, poloxamer 407 was slowly isolated at 1,500 rpm with agitator in 3°C purifi ed water and kept at 3°C for 12 h. The oil phase was prepared by completely dissolving poloxamer 407 using a hot plate set at 75°C at 250 rpm and keeping at room temperature for 12 h. Last , the polyol phase was performed. The aqueous phase at cold temperature was slowly added to the oil phase and stirred with agi-mixer at 1,800 rpm for 10 min. The polyol phase was gradually added to the mixture of the oil and water phases at 1,800 rpm for 10 min. Figure 1. Phase diagram of thermo-responsive polymers: (A) sol–gel transition and (B) volume transition (25). JOURNAL OF COSMETIC SCIENCE 328
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