ナノハイドロゲルを利用したペプチドの特殊放出制御型マイクロカプセルの設計(誌上シンポジウム)

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Biologically active peptides for therapeutic use have relatively short half-lives in general, requiring appropriate controlled-release systems for better therapy. Controlled release of peptides is, however, not as easy as that of conventional drugs because their large molecular size is much more dramatic in hindering the diffusion and release from polymeric devices. From this perspective, we have been developing two types of microcapsular devices containing new acrylate-based nanogels with a specific solute-permeability for delayed- or thermosensitive-release of peptide drugs. The microcapsule preparation was accomplished by an air suspension coating process. A nanogel-particle of acrylic terpolymer, ethyl acrylate-methyl methacrylate-2-hydroxyethyl methacrylate, was newly synthesized by emulsion polymerization to construct delayed-release microcapsules. By spray-coating the insulin-loaded lactose particles with the acrylic terpolymers, microcapsules showing a pH-independent delayed-release profile can be obtained. Oral administration of the microcapsules with the lag time of 6 hours to beagle dogs resulted in significantly reduced blood glucose concentration, leading to colon-specific insulin delivery with pharmacological availability of 5 %. Meanwhile, poly (N-isopropyl-carylamide) (p (NIPAAm)) nanogel-particles with a reversible temperature-dependent swelling property were prepared by dispersion polymerization to fabricate microcapsular membranes with thermosensitively changeable permeability. The microcapsules constructed by coating of drug-loaded CaCO_3 particles with a blend mixture of the p (NIPAAm) nanogels and ethylcellulose pseudo-latex exhibited an 'on-off' positively thermosensitive drug-release; the release rate was remarkably enhanced at higher temperatures possibly due to the formation of voids through the shrinkage of p (NIPAAm) nanogels in the membrane. A possible application of this type of microcapsules can be found in externally temperature-activated pulsatile peptide delivery.
公益社団法人日本薬学会の論文
2007-05-01

ナノハイドロゲルを利用したペプチドの特殊放出制御型マイクロカプセルの設計(誌上シンポジウム)

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