Saquinavir

In macrophages infected with Mycobacterium tuberculosis (Mtb) and/or HIV, the protease inhibitor saquinavir, but not ritonavir, increased endolysosomal protease activity, particularly cathepsin S. This led to intracellular killing of Mtb, improved HLA class II surface expression, enhanced T‑cell priming and proliferation, and increased IFN‑γ secretion. Saquinavir thus addresses both the bacterial pathogen and the host immune response. The authors propose saquinavir as a promising host‑directed therapy for tuberculosis, leveraging its dual effects on bacterial killing and antigen presentation.

Fig. 1 HIV PIs alter cathepsins’ activity in human macrophages infected with Mtb. (Pires D, et al., 2021)

Acetalated dextran electrospun fibers containing the protease inhibitor saquinavir were successfully fabricated and ground into “microconfetti,” unlike formulations using PLGA or polycaprolactone. By adjusting drug loading and polymer degradation rates, saquinavir release kinetics could be precisely tuned. In vivo, a single subcutaneous injection of microconfetti released saquinavir for over one week with high tissue retention. This injectable system overcomes the burst release and dose‑dumping risks associated with solid crystal long‑acting antiretrovirals, offering a flexible platform for sustained delivery of hydrophobic small molecules.

Fig. 2 Scanning electron micrographs with scale bar indicating 5 µm for electrospun constructs fabricated from 71kDa acetalated dextran (Ace-DEX). (Collier MA, et al., 2016)