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| TITLE | Hydroxypropyl β cyclodextrins effects on self-assembly of cyclic peptide, lanreotide acetate, in water and subsequent release rate from an in vitro emulator of subcutaneous delivery |
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| AUTHOR | Negar Jafari a , Camille Addison b , Hao Lou a , Michael J. Hageman a c |
| YEAR | 2024 |
| JOURNAL | Journal of Pharmaceutical Sciences |
| ABSTRACT | Most of the peptide drugs are often delivered subcutaneously. The significant barrier in this type of peptide administration is the high concentration of formulation, which can lead to self-assembly and aggregation. These phenomena can negatively impact the peptide drug's bioavailability, manufacturing, and injectability. This study investigated the self-assembly behavior of Lanreotide acetate at high concentrations in water using Hydroxypropyl β- Cyclodextrins (HPβCyD) to mitigate the self-assembly and enhance release rate during subcutaneous administration. Our finding demonstrated that the lanreotide/ HPβCyD inclusion complex effectively prevents aromatic-aromatic interactions of lanreotide, thereby controlling self-assembly. This complexation also alters the viscosity behavior of lanreotide from non-Newtonian under low shear rates to Newtonian solution. Furthermore, the lanreotide/ HPβCyD inclusion complex reduces interactions with hyaluronic acid in the subcutaneous environment, leading to significant improvement in the release rate of lanreotide acetate at high concentrations (above 3 % w/w in water). |
| FULL ARTICLE | https://www.sciencedirect.com/science/article/pii/S0022354924005380#keys0001 |
| INSTRUMENT | J-720 |
| KEYWORDS | Cyclodextrin(s), Complexation, Peptide(s), Peptide delivery, ViscosityDiffusion |
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