We focused on poly(acrylic acid) (PAA) as a mucoadhesive polymer. PAA is a synthetic polymer originally known for its strong adhesion to biological mucosa and has been extensively studied in the field of drug delivery systems (DDS). However, due to its high water solubility, the use of PAA as a base material was limited.

To overcome this, we turned our attention to a water-insoluble polymer complex formed by mixing PAA with polyvinylpyrrolidone (PVP). When aqueous solutions of PAA and PVP are mixed, they instantly bind together to form a polymer complex. However, this complex quickly becomes hydrophobic and precipitates as a white solid. As a result, the complex no longer dissolved or swelled in water, nor did it retain its adhesive properties, making it unsuitable for use as a tissue-adhesive material.

This insoluble and unswellable complex formation is attributed to hydrophobic interactions between the two polymers. Although hydrophobic interactions are individually weak, when multiple interaction points occur along the polymer chains, they collectively create an apparently strong association, resulting in a complex that neither dissolves nor swells in water.

For multiple hydrophobic interactions to occur between polymer chains, the chains must move freely and align themselves in an orderly fashion, much like the interlocking mechanism of a zipper. This dynamic alignment typically takes place when the polymers are mixed in aqueous solution. We hypothesized that by interfering with this dynamic alignment process, the formation of hydrophobic interactions could be suppressed. swelled slowly and formed a soft, bio-adhesive hydrated gel in water. When applied to water-moistened intestinal tissue, the mixture swelled on the surface and adhered strongly to the mucosa.

Because both PAA and PVP are widely used and recognized as safe pharmaceutical and food additives, we saw potential for this adhesive material to be used in controlled-release suppositories and other bioadhesive medical applications.

However, because this base contains a substantial amount of lipid components, the resulting composite swelled in water but also allowed the embedded oils to leach out during the swelling process, limiting the material's broader application. For years, we searched for a way to create a PAA/PVP adhesive complex that did not release oil.

At last, our long-standing goal was realized through an entirely new strategy: a solid-liquid interfacial mixing method: a solid–liquid interfacial mixing method. In this approach, an aqueous solution of PAA is poured into a container and completely dried to form a PAA film adhered to the container surface. When an aqueous solution of PVP is subsequently added, the PAA gradually dissolves from the film and forms a complex with PVP. During this process, the PAA chains are confined within the semi-solid, swelling gel matrix, preventing them from moving freely. As a result, the chains cannot align in an orderly, zipper-like fashion, which inhibits the formation of hydrophobic interactions. This allows the complex to form a highly swollen hydrogel that remains hydrophilic.

When this hydrogel is air-dried, it becomes a transparent film. Alternatively, freeze-drying the hydrogel yields a soft, sponge-like material. In both forms—the film and the sponge—the complex instantly rehydrates upon the addition of water, becoming a soft, transparent hydrogel that exhibits strong adhesion to biological tissues. The swellable, tissue-adhesive polymer complex obtained through this solid–liquid interfacial mixing method is what we call Wispecs.

In recent years, we have expanded the solid-liquid interfacial mixing technique to other polymer systems. As a result, we have successfully developed new water-swellable and bioadhesive polymer hydrogels from polymer pairs that typically yield insoluble and non-swellable complexes under conventional mixing conditions.

We are dedicated to continuously refining and expanding Wispecs technology to contribute to the development of safe and effective materials for next-generation medical applications.