Skin care polymer trends: marketers and suppliers alike are patenting innovative concepts in moisturizing and anti-wrinkle benefits using a variety of novel substances.

INNOVATION IN PERSONAL care products is continuing unabated. There are claimed breakthroughs in moisturizing and anti-wrinkle benefits using hyalurans, polymers for deposition, controlled delivery and release of therapeutic agents and fragrances; starburst polymers for precise gel formation, silicone acrylates for compatibility in polar formulations; and ingredients for structuring and stabilizing hydrophobic compositions. This article is based on recently published patent applications that highlight key trends in the use of polymers for skin care.

Moisturizing and Wrinkle-Free

Glycosaminoglycans are the most abundant heteropolysaccharides in the human body. They are unbranched, negatively charged polyelectrolytes consisting of linked disaccharide units that adopt extended conformations in solution to confer high viscosities on aqueous compositions. Hyaluronan is an example of a glycosaminoglycan. High molecular weight hyaluronan has been used for a number of years as a moisturizer for skin treatments. Low molecular weight hyaluronan has been reported to exhibit anti-wrinkle properties. A single mixture containing both high molecular weight and low molecular weight hyaluronans has now been claimed as a moisturizing, cosmetic and anti-wrinkle composition. (1)

Controlled Delivery

Another class of polysaccharides are the cyclodextrins. The cyclodextrins are cyclic polysaccharides that are capable of forming host-guest complexes with other molecules ranging, for example, from odors to fragrances to drug actives (Figure 1).

Cyclodextrins are cyclic polysaccharides made up of common, naturallyoccurring D-(+)- glucopyranose units joined by [alpha]-(1,4) linkages. The most common cyclodextrin rings are made up of six units ([alpha]-cyclodextrin), seven units ([beta]-cyclodextrin), and eight units ([gamma]-cyclodextrin). The ring structure has an inner apolar cavity. The primary hydroxyl groups are situated on the inner side and the secondary hydroxyl groups are situated on the outer side. Cyclodextrins could be useful for the controlled delivery of small molecule therapeutic agents with poor pharmacological profiles.

For example, therapeutic agents with low aqueous solubility, or ones in which bioactive forms exist in equilibrium with inactive forms, or agents that must be "dribbled in" because they are toxic in high doses. The host/guest inclusion supra-molecular complexes formed by cyclodextrins alter the physical, chemical and biological properties of the conjugated molecules and help in their controlled introduction to the target substrate. Their use in drug delivery is benefited by their good water-solubility, low toxicity and low immune response. Conjugates of drug molecules with polymer are another approach that has been used to circumvent the difficulties of delivering "problem" actives.

Polymers such as poly (hydroxypropylmethacrylate), poly(ethyleneglycol) and poly (-L-glutamic acid) have been used for this purpose. These approaches have been combined by covalently attaching cyclodextrin moieties to polymers by covalent attachment to polyvinyl alcohol or cellulose, or by copolymerization with vinyl acetate or methyl methacrylate (2) There have even been polymers made in which the polymer backbone is threaded though the cyclodextrin rings. (3) Biocompatible, water-soluble polymers containing covalently attached cyclodextrin moieties have been disclosed for the purpose of conjugating guest molecules by attachment that can be cleaved under biological conditions. (4) These cyclodextrin-containing polymers improve drug stability and solubility, and reduce toxicity of the small molecule therapeutics when used in vivo. Moreover, by selecting from a variety of linker groups and targeting ligands, the polymers can provide controlled delivery of therapeutic agents.

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Amphipathic block copolymers are large-scale analogues of surfactants. They adsorb strongly at interfaces and self-assemble to form micelles and complex, well-defined mesomorphic structures. These polymers thicken aqueous solutions to form viscoelastic gels. (5.6) The compositional scope of such block copolymers has been greatly increased with the advent of living free radical polymerization which allows fine control of the uniformity of molecular weight and the sequence in which the monomer units can be attached to the growing macromolecule during synthesis. Hydrogels can be formed without covalent cross links from such amphipathic block copolymers because the aggregated hydrophobic blocks can act as junction zones within the structure. Such hydrogels can offer advantages in processing and in "self-healing" properties whereby junction zones that are disrupted by shear or extension may reform in the quiescent state. Moreover, these amphipathic block copolymers can allow tailoring of physical and mechanical properties, and also control water adsorption and transmission. This is done by adjusting the size and number of blocks. A recent patent application claims copolymers constructed of hydrophobic blocks, hydrophilic blocks such as acrylic acid, and middle blocks, for example, of short alkyl chain methacrylate such as butyl methacrylate. (7) It was disclosed that the water content of these hydrogels could be adjusted by changing the pH.

Dendritic Polymer Gels

Another use for amphipathic polymers is in iontophoresis gels. Transepidermal delivery of substances can be greatly enhanced by iontophoresis. Iontophoresis involves applying a potential, from a small battery, across the skin to accelerate the intrusion of substances that are held in a reservoir that is attached to one electrode of the electric cell (Figure 2).

Better control of the intrusion of active substances should be realized if they are contained within a well-defined gel within the reservoir. A recent patent proposes the use of highly branched polymers for this purpose. The highly branched polymers are either dendrimers or arborols. The words "dendrimer" (8) (coined by Tomalia) and "arborol" (9) (coined by Newkome) are derived from the Greek dendro (meaning tree-like) and the Latin arbor (meaning tree). This nomenclature aptly describes the fractal-like branched structures of these molecules. Dendrimers and arborols are prepared by a series of iterative steps, each designed to add one sequence of successive segmental units to the outside of the molecule. Each sequence is called a "generation" in dendrimer-speak. Dendrimers can be constructed by a divergent synthesis or a convergent synthesis. Divergent construction starts with the core of the molecule and builds out generation by generation. In convergent construction, the branches are assembled first then they are brought together and bound by the core. Dendrimers and arborols are more precise branched molecules than hyperbranched polymers. Hyperbranched polymers, first patented by Kim in 1987. (10, 11, 12) are prepared in a single-pot process and, as a consequence, the individual molecules within the product vary in molecular weight and structure.

Amphipathic arborols are capable of self-assembling into micelles. (13) An example of such an arborol is shown in Figure 3 on the next page.

The molecule shown has a hydrophilic head consisting of nine hydroxyl groups and a hexyl chain as the hydrophobic tail. This molecule would be named [9]-6 arborol; the 9 refers to the number of hydroxyl groups and the 6 refers to the hydrophobic chain length. The solubility of one-directional arborols in water decreases dramatically with increasing length of the alkane hydrophobic group, from 13.0 mmol/L when n is 6, to 1.4 mmol/L when n is 8, to less than 0.017 mmol/L when n is 9. for [9]-n arborols. (14) At concentrations significantly higher than the critical micelle concentration, there is a possibility that amphipathic arborols would form gels by hydrophobic association and, if they did, the gels might be expected to have a more uniform pore size than conventional polymer gels. This could be the reason that these interesting tree-like molecules are being proposed for use in iontophoresis reservoirs to enhance the selectivity of delivery of active substances across the skin. (15)

Enhanced Fragrance Delivery