Pharmacokinetics and Biodisposition of Poly(vinyl alcohol) in Rats and Mice

Kaneo, Yoshiharu; Hashihama, Shiori; Kakinoki, Atsufumi; Tanaka, Tetsuro; Nakano, Takayuki; Ikeda, Yuka

doi:10.2133/dmpk.20.435

Cited by 63 publications

(45 citation statements)

References 23 publications

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“…PVA also provide a potential targetable drug delivery system. 15) Drug-polymer conjugates are potential candidates for the selective delivery of antineoplastic agents to tumor tissue. Incorporating acid-sensitive bonds between the drug and the polymer is an attractive approach because it ensures effective release of the polymer-bound drug at the tumor site.…”

mentioning

confidence: 99%

Synthesis of Poly(vinyl alcohol)-Doxorubicin Conjugates Containing cis-Aconityl Acid-Cleavable Bond and Its Isomer Dependent Doxorubicin Release

Kakinoki

Kaneo

Ikeda

et al. 2008

Biological & Pharmaceutical Bulletin

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Aconityl-doxorubicin (ADOX) was synthesized by the modified method of Shen and Ryser. Two isomers of cis-ADOX (cis-configuration) and trans-ADOX (trans-configuration) were generated in the reaction of DOX and cis-aconitic anhydride. These products were separated completely by using HPLC and analyzed by TOF-MS spectroscopy and 1 H-and 13 C-NMR experiments. The yields of cis-ADOX and trans-ADOX were 36.3 and 44.8%, respectively. The free g g-carboxylic group of ADOX molecule was coupled to poly(vinyl alcohol) (PVA) via ethylenediamine spacer, resulting the macromolecular conjugates of PVA-cis-ADOX and PVA-trans-ADOX, respectively. The DOX content of the conjugates estimated by the hydrolysis method detected the aglycone of DOX which can be estimated as the PVA-bound DOX selectively was 4.4 w/w% which was similar to 4.6 w/w% by the ordinary UV method. Both PVA-cis-ADOX and PVA-trans-ADOX were very stable at neutral pH, but the release of DOX was increased markedly under acidic conditions. Half-life of the release of DOX from PVA-cis-ADOX at pH 5.0 was 3 h which was 4.7-fold shorter than that from PVA-trans-ADOX (14 h). The cytotoxicities of PVA-cis-ADOX and PVA-trans-ADOX were evaluated by using J774.1 cells employing a [ 3 H]uridine incorporation assay as a measure of RNA synthesis. A significant difference in antitumor activity between PVA-cis-ADOX and PVA-trans-ADOX was observed where the former was much active than the later. It was suggested that the conjugate enters the cells and reaches the lysosomal/endosomal compartment, and that the aconityl spacer releases DOX from the conjugate in the acidic compartment of lysosomes/endosomes due to the participation of a free carboxylic group.

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confidence: 99%

Synthesis of Poly(vinyl alcohol)-Doxorubicin Conjugates Containing cis-Aconityl Acid-Cleavable Bond and Its Isomer Dependent Doxorubicin Release

Kakinoki

Kaneo

Ikeda

et al. 2008

Biological & Pharmaceutical Bulletin

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“…49 Studies examining the fate of larger molecular weights of PVA have shown accumulation within the liver and spleen of rats. 50 From these collective studies it is clear that the molecular weight of the polymer should be as low as possible to ensure complete elimination. To date most studies have focused on intravenous administration of polymers and therefore in order to license a dissolvable microneedle product further investigation into the distribution and elimination following repeated intradermal (i.d.)…”

Section: Discussionmentioning

confidence: 99%

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Cole

McCaffrey

Ali

et al. 2016

Human Vaccines & Immunotherapeutics

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DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.

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“…Functionalizing of PVA with FITC to make fluorescein-labeled PVA (F-PVA) was modified from Kaneo et al 23 with small alterations and can be seen in Fig. 1.…”

Section: Functionalization Of Polyvinyl Alcoholmentioning

confidence: 99%

Mechanically switchable polymer fibers for sensing in biological conditions

et al. 2017

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Abstract. The area of in vivo sensing using optical fibers commonly uses materials such as silica and polymethyl methacrylate, both of which possess much higher modulus than human tissue. The mechanical mismatch between materials and living tissue has been seen to cause higher levels of glial encapsulation, scarring, and inflammation, leading to failure of the implanted medical device. We present the use of a fiber made from polyvinyl alcohol (PVA) for use as an implantable sensor as it is an easy to work with functionalized polymer that undergoes a transition from rigid to soft when introduced to water. This ability to switch from stiff to soft reduces the severity of the immune response. The fabricated PVA fibers labeled with fluorescein for sensing applications showed excellent response to various stimuli while exhibiting mechanical switchability. For the dry fibers, a tensile storage modulus of 4700 MPa was measured, which fell sharply to 145 MPa upon wetting. The fibers showed excellent response to changing pH levels, producing values that were detectable in a range consistent with those seen in the literature and in proposed applications. The results show that these mechanically switchable fibers are a viable option for future sensing applications.

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Pharmacokinetics and Biodisposition of Poly(vinyl alcohol) in Rats and Mice

Cited by 63 publications

References 23 publications

Synthesis of Poly(vinyl alcohol)-Doxorubicin Conjugates Containing cis-Aconityl Acid-Cleavable Bond and Its Isomer Dependent Doxorubicin Release

Synthesis of Poly(vinyl alcohol)-Doxorubicin Conjugates Containing cis-Aconityl Acid-Cleavable Bond and Its Isomer Dependent Doxorubicin Release

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Mechanically switchable polymer fibers for sensing in biological conditions

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