Acute Immunocompatibility Profiling of Linear Poly(FTC) for Long-Acting Emtricitabine Delivery

Background/Objectives: Long-acting therapeutics are being investigated for their potential to enhance medication adherence and improve overall treatment outcomes. Due to the prolonged residence time at the administration site, such as subcutaneous insertion, long-acting preparations may modulate the responses of local immune cells linked to material characteristics. Long-acting Polymer of Prodrug (POP) of Nucleoside Reverse Transcriptase Inhibitor (NRTI) Emtricitabine (FTC) has been developed for subcutaneous administration. Methods: The present study focused on the acute immunocompatibility of an FTC-based POP and its interactions with various cells and components of the immune system following acute exposure using DMSO-dispersed polymer linear poly(FTC). A tiered assessment was carried out, including assessment of pyrogens (MAT), cytotoxicity (MTT/LDH), Leukocyte proliferation (MTT), complement proteins (iC3b, Factor H, sC5b-9, Bb and C4d EIAs) and cytokine secretion in whole blood (Luminex panel). Results: Linear poly(FTC) had no detectable pyrogenic activity, no overt cytotoxicity within the THP-1 cell line, no consistent leukocyte proliferative activation and no broad whole-blood cytokine induction. Complement analysis, however, indicated a concentration-associated higher iC3b signal by linear poly(FTC) and a higher Bb signal by linear poly(FTC) at 80 µg/mL when compared to vehicle (0.4% DMSO). Conclusions: Further investigations are warranted to assess the long-term implications of these implants, given their extended residence times. Therefore, the adaptation of existing safety assessments should be prioritized to facilitate the safe translation of these POPs into clinical studies.