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The Effect of Cholesterol Content on the Adjuvant Activity of Nucleic-Acid-Free Lipid Nanoparticles.
Anindita, Jessica; Tanaka, Hiroki; Yamakawa, Takuma; Sato, Yuka; Matsumoto, Chika; Ishizaki, Kota; Oyama, Taiji; Suzuki, Satoko; Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu; Sasaki, Kasumi; Ogura, Yumika; Yonemochi, Etsuo; Sakurai, Yu; Hatakeyama, Hiroto; Akita, Hidetaka.
Afiliación
  • Anindita J; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan.
  • Tanaka H; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Yamakawa T; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan.
  • Sato Y; Center for Advanced Modalities and DDS, Osaka University, Suita 565-0871, Osaka, Japan.
  • Matsumoto C; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Ishizaki K; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Oyama T; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan.
  • Suzuki S; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Ueda K; Sales Division, JASCO Corporation, 2967-5 Ishikawa, Hachioji City 192-8537, Tokyo, Japan.
  • Higashi K; Applicative Solution Lab Division, JASCO Corporation, 2967-5 Ishikawa, Hachioji City 192-8537, Tokyo, Japan.
  • Moribe K; Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Sasaki K; Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Ogura Y; Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-0856, Chiba, Japan.
  • Yonemochi E; Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Shinagawa City 142-8501, Tokyo, Japan.
  • Sakurai Y; Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Shinagawa City 142-8501, Tokyo, Japan.
  • Hatakeyama H; Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Shinagawa City 142-8501, Tokyo, Japan.
  • Akita H; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai City 980-8578, Miyagi, Japan.
Pharmaceutics ; 16(2)2024 Jan 26.
Article en En | MEDLINE | ID: mdl-38399242
ABSTRACT
RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adjuvant activity continue to require clarification. To characterize the relationships between the lipid composition, particle morphology, and adjuvant activity of LNPs, the nanostructures of LNPs and their antibody production were evaluated. To simply compare the adjuvant activity of LNPs, empty LNPs were subcutaneously injected with recombinant proteins. Consistent with previous research, the presence of ionizable lipids was one of the determinant factors. Adjuvant activity was induced when a tiny cholesterol assembly (cholesterol-induced phase, ChiP) was formed according to the amount of cholesterol present. Moreover, adjuvant activity was diminished when the content of cholesterol was excessive. Thus, it is plausible that an intermediate structure of cholesterol (not in a crystalline-like state) in an intra-particle space could be closely related to the immunogenicity of LNPs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza