Formulation stability of amphiphilic poly(γ-glutamic acid) nanoparticle and evaluation of cardiotoxicity of NPs with human iPSC derived 3D-cardiomyocyte tissues.

We conducted a stability study of biodegradable and amphiphilic nanoparticles (NPs) consisting of phenylalanine attached poly(γ-glutamic acid) (γ-PGA-Phe) for drug delivery to find the optimal formulation, and define the optimal storage conditions using novel quantitative analytical methods. The stability of NP suspension and lyophilized NP powder manufactured by a dimethyl sulfoxide (DMSO)-based and an ethanol (EtOH)-based process was assessed under 5°C, 25°C/60% relative humidity (RH) and 40°C/75%RH. The content of γ-PGA-Phe, impurities, absolute molecular weight, appearance, clarity of solution, particle size, zeta potential, particle matter, osmolality, water content and pH were evaluated as parameters of NP stability. Lyophilized NPs with trehalose showed better stability. The lyophilized NP formulation could therefore provide a stable and high quality product for clinical studies and shows promise as an effective drug delivery system carrier. The cardiotoxicity of prospective impurities contained in NPs and reagents used in the manufacturing process with human induced pluripotent stem cells (hiPSC) derived three-dimensional (3D)-cardiomyocyte (CM) tissues by centrifugation Layer-by-Layer technique (LbL) was also evaluated. As a result, cardiotoxicity for NPs and reagents was not observed and it was clarified that the potential risk to human safety from NPs is low. The applicability of the approaches with hiPSC derived 3D-CM tissues by centrifugation LbL is will be evaluated.

• Publication year

  2020

• Venue

  Journal of Pharmacy and Science

• Publication date

  2020-02-15

• Fields of study

  Medicine, Materials Science, Chemistry, Engineering

• Identifiers
  DOI 10.1016/j.xphs.2020.01.032PMID 32070703
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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