Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm l...Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm length and 300 μm diameter at the bottom. Long-term stability and dissolution studies were performed by HPLC method. Pharmacokinetic and pharmacological evaluations were performed after administration of bFGF loaded DMs to rats. Results: The bFGF contents were 2.15 ± 0.07, 1.07 ± 0.04, 0.56 ± 0.07 and 0.12 ± 0.03 μg. The 100.2 ± 3.4%, 100.2 ± 3.3%, 99.3 ± 1.4% and 100.4 ± 3.0% of bFGF were recovered after 1, 3 and 6 months and 1 year incubation at 40°C. The bFGF was released from DMs within 5 min. In a pharmacokinetic study using 2.0 and 1.0 μg bFGF-loaded DMs, no systemic exposure of bFGF was detected. The initial bFGF concentrations in the rat skin tissue after administration of bFGF-loaded DMs to the hair-removed rat abdominal skin were 510.2 ± 20.1 ng/g wet weight for 2 μg bFGF DMs and 264.2 ± 56.5 ng/g wet weight for 1 μg DMs, declining slowly thereafter to 226.3 ± 33.5 and 105.1 ± 27.4 ng/g wet weight at 6 hr after administration. Good dose-dependency was observed. Pharmacological evaluation of bFGF-loaded DMs of 2.0, 1.0, 0.5, and 0.1 μg, in the wound healing rat model, all used DMs, but 0.1 μg DMs, showed good healing effects. Considered collectively, these results suggest the usefulness of bFGF-loaded DMs for local therapy of skin wound disease.展开更多
In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles intr...In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.展开更多
文摘Purpose: The usefulness of dissolving microneedles (DMs) for local skin therapy by basic fibroblast growth factor (bFGF) was studied in rats. Methods: We prepared four kinds of bFGF-loaded DMs, approximately 500 μm length and 300 μm diameter at the bottom. Long-term stability and dissolution studies were performed by HPLC method. Pharmacokinetic and pharmacological evaluations were performed after administration of bFGF loaded DMs to rats. Results: The bFGF contents were 2.15 ± 0.07, 1.07 ± 0.04, 0.56 ± 0.07 and 0.12 ± 0.03 μg. The 100.2 ± 3.4%, 100.2 ± 3.3%, 99.3 ± 1.4% and 100.4 ± 3.0% of bFGF were recovered after 1, 3 and 6 months and 1 year incubation at 40°C. The bFGF was released from DMs within 5 min. In a pharmacokinetic study using 2.0 and 1.0 μg bFGF-loaded DMs, no systemic exposure of bFGF was detected. The initial bFGF concentrations in the rat skin tissue after administration of bFGF-loaded DMs to the hair-removed rat abdominal skin were 510.2 ± 20.1 ng/g wet weight for 2 μg bFGF DMs and 264.2 ± 56.5 ng/g wet weight for 1 μg DMs, declining slowly thereafter to 226.3 ± 33.5 and 105.1 ± 27.4 ng/g wet weight at 6 hr after administration. Good dose-dependency was observed. Pharmacological evaluation of bFGF-loaded DMs of 2.0, 1.0, 0.5, and 0.1 μg, in the wound healing rat model, all used DMs, but 0.1 μg DMs, showed good healing effects. Considered collectively, these results suggest the usefulness of bFGF-loaded DMs for local therapy of skin wound disease.
文摘In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.
