February 8, 2019

Mandom successfully develops highly
skin-permeable fine capsule formulation “bicelles”~ For the development of skin care products with greater functionality ~Mandom Corporation (hereafter, called Mandom; headquartered in Osaka city; president executive officer anddirector Motonobu Nishimura) has been involved in capsule formulation research with the aim to develop skin careproducts that have greater functionality. Studies of advanced capsule formulations, which are superior and havehigher permeability than conventional capsule formulations, and the use of a specific component of bilayer
membrane led Mandom to the successful creation of the capsule formulation “bicelles,” which is superior toconventional capsule formulations. The skin permeability of bicelles is confirmed to be high.
1. What is bicelle?
Conventionally, capsule formulations studied in the cosmetics industry include liposomes. A liposome has aspherical-like structure composed of many layers of bilayer membranes, consisting mainly of phospholipids
overlapping in a radial pattern. Liposomes range in size from approximately one-hundred to a few hundred
nanometers (Figure 1). A bicelle also consists mainly of phospholipids and has a spherical-like structure composedof overlapping bilayer membrane discs. However, it ranges in size between a few nanometers to tens of nanometers,
which is considered the smallest among capsule formulations that contain a lipid bilayer structure (Figure 2).
Bicelles has been used mainly as an in vivo membrane model for the assessment of pharmacological activity,
toxicity, and pharmacokinetics of a new drug, but only a few research programs in the cosmetics industry havefocused on the skin penetration function of bicelles.
2. Development of bicelles that can be applied in cosmetics
Two different types of phospholipids are usually used in bicelles, although a special processing requirement has
made its application in cosmetics difficult. Mandom successfully created this form of bicelles, which can be used incosmetics owing to the combination of phospholipid components suitable for cosmetic applications and different
types of amphiphilic components (*1).
3. Bicelles has higher skin permeability than conventional liposomes
Bicelles and liposomes were evaluated in the human skin to compare their skin permeability. The results
showed that the skin permeability rate of bicelles was faster than that of liposomes (Figure 3).
4. A model serum prepared with bicelle technology penetrated deep into the stratum corneum
A skin penetration test was performed by using TOF-SIMS(*2) in the human skin to evaluate a model serum
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-1-that applied the bicelle technology. It was demonstrated that the model serum penetrated deep into the stratum
corneum (Figure 4).

Mandom aims to apply the bicelle technology that was developed through the present research in thedevelopment of skin care products with excellent skin permeability.

*1 An amphiphilic component is made up of parts that easily blend with both oil and water.
*2 TOF-SIMS (time-of-flight secondary ion mass spectrometry)An analysis method used to identify the presence of target molecules. The sample is irradiated with an ion
beam, and the ions released from the surface of the sample are measured.

REFERENCES
Figure 1. Liposome structure and electronmicroscopic image

Figure 2. Bicelle structure and electron
microscopic image

Phospholipid
Hydrophilic part
Hydrophobic part

MODEL USED FOR IMAGING: Transmission electron microscope (JEM-1400Plus)
CCD CAMERA: EM-14830RUBY2TECHNIQUE: Negative staining method-2-Slow

BicelleLiposome

Permeability
rate

Fast

Cumulative mass of caffeine permeated into the skin (μg)

Figure 3. Comparison of skin permeation of bicelle and liposome

Duration of processing (h)Female, 44 years of age, skin thickness: 500 (400–600) μm, confirmation of healthy skin: 20 g/m per2SKIN SAMPLE:

hour or less by TEWLEVALUATION METHOD: Amount of caffeine permeated into the skin from the stratum corneum to the dermal layer wasquantitated by using an evaluation system called a Franz Cell (1.5 cm diameter, approximately 6.5 mL
receiver volume [Hanson research]) (n=5).

Figure 4. Evaluation of the skin permeation of a model serum prepared with bicelle technology

Stratum corneum side

Shallow

Epidermis

Deep

Cell layer side

SKIN SAMPLE:

Female, 33 years of age, skin thickness: 500 (400–600) μm, confirmation of healthy skin: 20 g/m2per hour or less by TEWLEVALUATION METHOD:A model serum was applied on the human skin. Skin cross sections were measured after 24 hours
by using TOF-SIMS to evaluate the skin permeability of the model serum.

MEASURING CONDITIONS: Measuring device: TOF-SIMS, mass spectrometer: time-of-flight secondary ion mass spectrometry,primary ion: BiEnd-3-