Skincare: Polymer micelles

Kunio Shimada, Koji Awai, Hiroki Fukui & Nobuyuki Yamamoto describe new liposome and polymer micelle technology using MPC/SMA copolymer as a drug delivery system with cosmetic applications

The various functions of whitening, anti-ageing and other activities are regular requirements of cosmetics today. The development of application technology in the form of drug delivery systems (DDS) for cosmetics is therefore a

very important area. One option is a polymer micelle consisting of phospholipids and 2-methacryloyloxyethyl phosphorylcholine (MPC)/stearyl methacrylate (SMA) copolymer [INCI: Polyquaternium-61].

Polymer micelle is a DDS technology that is attracting a lot of attention. Polymer micelles, which are no larger than 100nm, have the potential to accumulate at solid cancer loci due to their enhanced permeation and retention (EPR) capacities. Nippon Kayaku[1] has developed a polymer micelle that has anti-cancer adriamycin (ADR) bound to the aspartate group of a polymer of polyethylene glycol and polyaspartic acid. In a test against mice solid cancer, even a maximum permitted dosage of ADR showed no reduction in cancer size when no micelle polymers were used. However, dramatic cancer suppression was shown when ADR was enclosed in polymer micelles, even with an amount smaller than the maximum allowed dosage.

It is possible that an ideal anti-cancer drug system has been developed that releases the effective component but only at the target cancer site and never in the blood by utilising a temperature-responsive polymer derivative of N-isopropyl acrylic amide, which suddenly becomes hydrophobic at and above a certain temperature. The temperature at which ADR is spontaneously released, which is usually 32°C, can be adjusted by controlling the components of the temperature-responsive polymer. Setting the temperature at a level higher than the body temperature and combining the system with hyperthermic oncology, which involves heating parts of the body, will enable the development of a multiple targeting system.

Cosmetic applications

There are radical copolymers that are made from long alkyl chains

of 2-methacryloyloxyethyl phosphorylcholine (MPC) and stearyl methacrylate (SMA) (Figure 1). Yamamoto et al[2] reported that a copolymer containing at least 30 mol% of SMA formed micelles of 10 to 40nm in diameter within a water

solvent, although the copolymer itself was water insoluble (Figure 2). A polymer ratio of MPC/SMA=50/50 (mol ratio) showed the highest solubilization efficacy. A nano dispersion of the copolymer formed a lamellar structure of 6nm spontaneously (Figure 3) when dried. There was a report mentioning the possibility of using the copolymer for skin care since the intercellular lipids of human stratum corneum also has a lamellar structure.[3]

The polymer micelle [trade name: Lipidure-NR, produced by NOF Corporation] requires no additional shearing energy because it is dispersed in a self-organised manner. It needs no special emulsifiers to make a nano dispersion and it is more stable against heat and surfactants than ordinary liposome micelles. It is highly safe because it is less cytotoxic than

physiologically active single-chained lysophospholipids and polyglycerol fatty acid esters. Double acyl chains, such as ceramide, have no cytotoxicity, but have a smaller water holding capacity than phospholipid polymers. Fukui et al[4] reported that the polymer micelle was effective in caring for the skin and hair.

A test on the penetration of the polymer micelle into the hair was conducted as described here. Specimens of damaged hair were soaked in solutions containing the polymer micelle and no polymer micelle for one minute, rinsed three times with water and then dried. The specimens were embedded in cryostat and sliced into sections of 5 micrometres. The hair fibres were observed under a fluorescent microscope (exposure time: lightness 1/300 sec, fluorescence 2 sec, fluorescent probe; Nile Red [NIR, Ex=540 nm]). The results are shown in Figure 4. The fibres treated with the nano micelle solution, into which NIR was enclosed, showed stronger fluorescence than the specimens treated with the dispersed solution of NIR, not only at the surface but also on the inside. This suggests that using nano particles formed by the polymer micelle not only protected the surface of hair fibres but also enabled effective ingredients to be transmitted deep inside the hair fibres. It is anticipated that polymer micelles will be used as effective, stable drug delivery systems that enclose active cosmetic ingredients, such as oily vitamins.

References

1. Kataoka K, Nikkei Bio Business, 9, 49 (2003)

2. Yamamoto N et al, Polymer Preprint Japan, Vol 52, No 5, 1107 (2003)

3. Shimada K et al, SOFW, 9, 16 (2005)

4. Shimada K, Awai K & Fukui Y, Bio Industry, Vol 22, No 9 (2005)

Contact

Kunio Shimada,, NOF Corp, Japan

Email kunio_shimada@nof.co.jp