Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials.

Poly(ε-caprolactone) (PCL) hybrid sheets containing polymeric micelles: Effects of inner structures on the material properties of the sheets.

In the present paper, we clarify the effects that the composition of three types of sheets-the PCL sheet, the PCL-BC (PCL-block copolymer composite) sheet, and the PCL-PM (PCL-polymeric micelle composite) sheet-can have on (1) the sheets' inner structure, (2) the dispersity of hydrophilic compounds in the sheets, (3) the sheets' mechanical properties, and (4) the sheets' degradability. Our results show that (1) the PCL-PM sheet can disperse hydrophilic compounds uniformly, (2) the molecular state (free or micellar) of a co-existing compound (PEG-b-PCL block copolymers) affects the strength and the inner structures of the sheets, whereas the presence of a co-existing compound affects the flexibility of the sheets, and (3) according to our degradation experiment, hard-to-handle PCL having extremely low hydrolysis could serve as materials with a controllable surface morphology by the effective use of co-existing compounds. The results obtained in this paper show that the PCL-CM sheet, with its uniformly dispersed polymeric micelles providing hydrophilic spaces, could be an effective biomaterial platform for incorporating hydrophilic polymers.

Poly(ɛ-caprolactone) (PCL)-polymeric micelle hybrid sheets for the incorporation and release of hydrophilic proteins.

Sheets have several advantages over conventional gel- or particle-type drug carriers. Sheets have several notable attributes: sheets' size and shape are easily adjustable, sheets are highly accessible in surgery, and sheets have a large contact area relative to drug-targeting sites. However, it is difficult to incorporate hydrophilic proteins into hydrophobic sheets and to release the proteins over the long term in a sustained manner. In the present study, we show that "poly(ɛ-caprolactone) (PCL)-polymeric micelle hybrid sheets" can be used for the incorporation and release of hydrophilic proteins. Polymeric micelles (i.e., spaces that can incorporate hydrophilic compounds) are, in this study, uniformly dispersed in hydrophobic and biocompatible biomaterial sheet. We have clarified that the composition of block copolymer, methoxy-terminated poly(ethylene glycol)-block-poly(ɛ-caprolactone) (CH3O-PEG-b-PCL), can affect two variables: the stability of w/o emulsion and the release properties of the resulting sheets, by means of visual qualitative observations, newly developed quantitative analyses (advanced fractal analysis, advanced FD) based on deviation of the fractal dimension (FD), and release experiments. We clarified that the release behavior of BSA was affected by the composition of the block copolymers and the resulting emulsion. The results obtained in this paper show that the hydrophobic sheets in which polymeric micelles providing hydrophilic spaces were dispersed could be an effective platform for incorporating and releasing hydrophilic proteins.