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  • 1.  ADME/DMPK considerations for LNPs

    This message was posted by a user wishing to remain anonymous
    Posted 06-11-2023 13:39
    This message was posted by a user wishing to remain anonymous

    I am looking for an industry white paper, review paper, regulatory guidance, etc. on ADME/DMPK considerations for LNPs.



  • 2.  RE: ADME/DMPK considerations for LNPs

    Posted 06-12-2023 08:46
    Here is the link to FDA guidance on liposome products:

    Few reviews for RNA delivery and related LNPs
    Small interfering RNA (siRNA) is a promising drug candidate, expected to have broad therapeutic potentials toward various diseases including viral infections and cancer. With recent advances in bioconjugate chemistry and carrier technology, several siRNA-based drugs have advanced to clinical trials. ...
    pubmed.ncbi.nlm.nih.gov

    Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibit drug resistance due to activation of various cellular level processes viz. activation of drug ef ...
    pubmed.ncbi.nlm.nih.gov

    mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrat ...
    pubmed.ncbi.nlm.nih.gov
    In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and trea ...
    pubmed.ncbi.nlm.nih.gov
    Lipid nanoparticles (LNPs) have been recognized as efficient vehicles to transport a large variety of therapeutics. Currently in the spotlight as important constituents of the COVID-19 mRNA vaccines, LNPs play a significant role in protecting and transporting mRNA to cells. As one of their key const ...
    pubmed.ncbi.nlm.nih.gov

    There is a lot of information available. The ADME and DMPK characterization of LNPs typically involves evaluation of each component to determine if they are already considered as GRAS (generally regarded as safe), if their disposition is characterized. 
    When it's a novel excipient without information about its ADME already available, it can be characterized separately in animals to establish safety margin of exposure and organ distribution. When you know components of your LNP formulation, you can do a focused search for information for each one of them individually.
    PK of lipid components of LNPs in animals and humans can be quite unusual and frequently involves re-distribution between tissues with more than one peak and valley in the PK profile even after IV infusion.




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  • 3.  RE: ADME/DMPK considerations for LNPs

    This message was posted by a user wishing to remain anonymous
    Posted 06-13-2023 18:09
    This message was posted by a user wishing to remain anonymous

    Thank you, Galina! This is very helpful.


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