Ion-dependent slow protein release from in vivo disintegrating micro-granules.

Abstract

Through the controlled addition of divalent cations, polyhistidine-tagged proteins can be clustered in form of chemically pure and mechanically stable micron-scale particles. Under physiological conditions, these materials act as self-disintegrating protein depots for the progressive release of the forming polypeptide, with potential applications in protein drug delivery, diagnosis, or theragnosis. Here we have explored the in vivo disintegration pattern of a set of such depots, upon subcutaneous administration in mice. These microparticles were fabricated with cationic forms of either Zn, Ca, Mg, or Mn, which abound in the mammalian body. By using a CXCR4-targeted fluorescent protein as a reporter building block we categorized those cations regarding their ability to persist in the administration site and to sustain a slow release of functional protein. Ca2+ and specially Zn2+ have been observed as particularly good promoters of time-prolonged protein leakage. The released polypeptides result is available for selective molecular interactions, such as specific fluorescent labeling of tumor tissues, in which the protein reaches nearly steady levels.

• Authors: Patricia Álamo, Eloi Parladé, Hèctor López-Laguna, Eric Voltà-Durán, Ugutz Unzueta, Esther Vazquez, Ramon Mangues, Antonio Villaverde
• Journal: Drug delivery (Drug Deliv) Vol. 28 Issue 1 Pg. 2383-2391 (Dec 2021) ISSN: 1521-0464 [Electronic] England
• PMID: 34747685 (Publication Type: Journal Article)

Chemical References

• Cations, Divalent
• Drug Carriers
• Proteins
• Receptors, CXCR4
• polyhistidine
• Histidine

Topics

• Administration, Oral
• Animals
• Cations, Divalent (chemistry)
• Chemistry, Pharmaceutical
• Dose-Response Relationship, Drug
• Drug Carriers (chemistry)
• Drug Liberation
• Female
• Histidine (chemistry)
• Injections, Subcutaneous
• Mice
• Nanoparticles (chemistry)
• Particle Size
• Proteins (administration & dosage, pharmacokinetics)
• Receptors, CXCR4 (metabolism)
• Xenograft Model Antitumor Assays