Study on Design of Biodegradable Nanoparticles with Function of Controlled Drug Release

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The high polymer of repeating pentapeptide sequence, (VPGVG)n simply Vpp, is basis for phosphorylation-responsible and redox-responsible controlled release devices. Vpp undergoes self-assembly called coacervation, where coacervate droplets with diameter in the range of 400 to 600 nm are formed. The nanoparticles cross-linked by cobalt-60 γ-irradiation of coacervate droplets are useful as drug release devices. Vpp and random copolymers, [8(VPGVG), 2(VPGK(Z)G)] simply VK(Z)pp and [8(VPGVG), 2(VPGK(Boc)G)] simply VK(Boc)pp, where the molar ratio of VPGVG to VPGK(Z)G or VPG(Boc)G is 8 to 2 were synthesized. The coacervate droplets of these polymer and copolymers in the coacervate state at 55-60'C were cross-linked by cobalt-60 γ-irradiation to yield nanoparticles in the range of 200 to 400 nm. The nanoparticles obtained were stable in the treatment of enzyme. The loading antitumor drug, adriamycin, into Vpp-derived and VK(Boc)pp-derived nanoparticles were 80 and 77%, respectively. The release of adriamycin from Vpp-derived and VK(Boc)pp-derived nanoparticles were 13 and 19 days (time for releasing half amount of loaded drug), respectively. Next we synthesized two random copolymers, [30(VPGVG), (RGYSL)] and [7(V PGV G), 3 (VPGK(NMeN)G)], where RGYSL which is a peptide substrate for phosphorylation by protein kinase and VPGK(NMeN)G which is a redox peptide with N-methylnicotinamide were added. The onset temperature of self-assembly of [30(VPGVG), (RGYSL)] shifted to higher temperature by phosphorylation and to lower temperature by dephosphorylation. Moreover, the onset temperature of self-assembly of [7(VPGVG), 3(VPGK(NMeN)G)] shifted to higher temperature by oxidation and to lower temperature by reduction. Further study on controlled drug release from nanoparticles of [30(VPGVG), (RGYSL)] and [7(VPGVG), 3(VPGK(NMeN)G)] is underway.