Dry Powder Formulations for Messenger RNA
a technology of messenger rna and powder formulation, which is applied in the direction of spray delivery, peptide/protein ingredients, aerosol delivery, etc., can solve the problems of poor yield and unsatisfactory particle characteristics, and achieve the effect of more efficient mrna delivery, less undesirable particle characteristics, and more efficacy of mrna therapy
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example 1
Dry Powder Formulations Recovered from Spray-Drying
[0238]In this example, LNP-encapsulated mRNA formulations were prepared with and without polymer and spray-dried. The results show that the LNP-encapsulated mRNA formulations prepared with polymer provides an unexpected high recovery from the spray-dry process, as compared to the same mRNA-LNP formulations prepared without polymer.
[0239]In particular, two of LNP-encapsulated mRNA formulations (mRNA encoding Firefly Luciferase (FFL) and formulations referred to as FFL-F1 an FFL-F2, respectively) each were prepared without polymer or with polymer, with the individual compositions of each described in Table 1. To prepare these formulations for spray-drying, the FFL mRNA was first mixed with lipid nanoparticles (LNPs) using a gear pump in order to encapsulate the mRNA within the LNPs. Then, for the “With Polymer” samples, the polymer solution then was mixed with mRNA-LNPs using a gear pump. The solutions were then subjected to spray-dry...
example 2
and Stability of mRNA Dry Powder Formulations
[0242]In this example, two mRNA formulations encoding argininosuccinate synthetase or ASS1 mRNA were prepared and assessed for long-term stability. In particular, one mRNA formulation was prepared that included no LNP but did include polymer (ASS1-F1). A second mRNA formulation was prepared that included LNP-encapsulated LNP plus polymer (ASS-F2). Each formulation is described further in Table 2.
[0243]For the ASS1-F1 formulation, the mRNA was directly mixed with the polymer using a gear pump. For the ASS1-F2 formulation, the mRNA was first mixed with lipid nanoparticles (LNPs) using a gear pump in order to encapsulate the mRNA within the LNPs and then the polymer solution was mixed with the mRNA-LNPs using a gear pump. The final formulations were concentrated, and mannitol was added to each formulation. The solutions were then subjected to spray-drying as depicted in the graphical representation of the instrumentation in FIG. 1. The follo...
example 3
Method of mRNA Encapsulation in Lipid-Polymer Nanoparticle
[0253]In this example, lipids, mRNA and polymer were prepared in a single step to produce lipid-polymer-encapsulated mRNA nanoparticles (formulations ASS1-F3 With Polymer and ASS1-F4 With Polymer). This is in contrast to Example 1 and Example 2 where LNP-encapsulating mRNA nanoparticles were first prepared and then polymer was added into the formulation. In addition, reference formulations were prepared by the same process but without including polymer in the nanoparticle or formulation (formulations ASS1-F3 Without Polymer and ASS1-F4 Without Polymer).
[0254]In particular, lipids and polymer (or just lipids for the control formulations) were dissolved in ethanol and together mixed with mRNA solution using a gear pump. Four different formulations were prepared. The first and second formulations (ASS1-F3 Without Polymer and ASS1-F3 With Polymer) were prepared with cKK-E12 as the cationic lipid, either without or with polymer. T...
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