Skin permeability of tulobuterol in two transdermal formulations and their followability.

Various generic transdermal formulations of tulobuterol containing rubber and acrylate base polymers are commercially available in Japan. However, none of the formulations have been compared directly with respect to the skin permeability of tulobuterol and to their follow ability. Tulobuterol Tape Sawai of rubber base and Tulobuterol Tape NP of acrylate base were used to conduct the in vitro 24-hour skin permeability test of tulobuterol at receiver solution temperatures of 32°C, 37°C, and 40°C. Furthermore, the followability of these tapes were examined by measuring the depth of the pores that were formed in their adhesive layer. Consequently, the maximum flux of tulobuterol was greater for Tulobuterol Tape NP. Arrhenius plot analysis revealed that Tulobuterol Tape Sawai was more sensitive to skin surface temperature compared with Tulobuterol Tape NP. Skin abrasion had a greater effect on the skin permeability of tulobuterol in Tulobuterol Tape Sawai than in Tulobuterol Tape NP. Followability was greater for Tulobuterol Tape NP than for Tulobuterol Tape Sawai. These results suggest that a transdermal formulation of acrylate base is preferable to that with a rubber base when skin surface temperature varies or when the skin is abraded. In clinical settings, therefore, a formulation of acrylate base is preferable to a formulation of rubber base when skin surface temperature varies or when the skin is abraded. The formulation needs to be applied to the skin of less asperity for the achievement of better transdermal absorption of tulobuterol.

A novel peptide mimotope identified as a potential immunosuppressive vaccine for organ transplantation.

We reported that anti-histone H1 autoantibody is one of the main immunosuppressive factors in serum that is induced after orthotopic liver transplantation in a rat tolerogenic model. We generated a novel anti-histone H1 IgM mAb produced by hybridoma 16G9 (16G9 mAb) that shows MLR-inhibitory activity. Identification of a functional epitope responsible for the immunosuppressive activity of 16G9 mAb may lead to the establishment of a novel therapeutic strategy. We used a combinatorial phage display peptide library to screen for peptides that bind to 16G9 mAb. Consequently, two peptides that bind to 16G9 mAb, SSV and LPQ, were selected from the library. The binding of 16G9 mAb to histone H1 was inhibited by SSV. SSV was recognized by rat tolerogenic post-orthotopic liver transplantation serum and the binding to SSV was inhibited by histone H1. Mice were immunized with keyhole limpet hemocyanin-conjugated SSV and LPQ. Abs induced by SSV immunization inhibited Con A-stimulated splenocyte proliferation, and the inhibition was neutralized by preincubation with SSV. Splenocytes stimulated by anti-CD3 Ab were inhibited by SSV-induced Abs using CFSE labeling. SSV immunization in rats before heterotopic heart transplantation resulted in significant prolonged allograft survival. These findings suggested that SSV is a functional histone H1-binding epitope for 16G9 mAb. SSV is capable of determining serum immunoreactivity against histone H1 as an index marker for tolerance. The inhibitory activity of SSV-induced Abs on blast cell proliferation and the prolonged graft survival that results from SSV immunization imply a potential for the development of an immunosuppressive vaccine.