Injection volumes: possible role of
recombinant hyaluronidase and other approaches

Speaker: Nicole C. Ammerman, Center for Tuberculosis Research at JHU

Discussed the potential role of recombinant hyaluronidase to modify injection volumes of long-acting injectable (LAI) formulations. 

Achieving an effective dose and exposure profile with a tolerable total injection volume is a key limitation in development of LAIs.
Subcutaneous (SC) administration is preferred over intramuscular (IM), as the SC route involves less discomfort and allows for repeat dosing via self-administration. However, small SC injection volumes do not support most LAIs, including CAB and RPV. 

Hyaluronic acid limits SC injection volumes. 
Hyaluronic acid prevents fluid dispersion through the extracellular matrix and resists compressive forces created by the LAI drug depot. In contrast, hyaluronidase temporarily depolymerizes hyaluronic acid and promotes fluid dispersion.

Hyaluronidase allows larger SC injection volumes, but may impact PK. 
Studies of LAI paliperidone palmitate (PP-LAI) co-administrated with hyaluronidase in a rat model suggest that granuloma formation around the LAI drug depot may affect plasma exposure. 

A pilot study of PP-LAI is underway in mouse (JHU) and rat models (University of Liverpool). 
The study aims to document the host inflammatory response and release kinetics of PP-LAI co-administered with hyaluronidase. Endpoints are the histology surrounding the PP-LAI drug depot in muscle tissue and blood sampling up to 4 weeks post injection. 

Future implications of the pilot study. 
If there is no impact on drug release, then other LAI formulations will be tested and ultimately compared with other antimicrobial formulations. 

[Return to 2021 LEAP Workshop Menu]