Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice

This is the authors' abstract. We don't add key points for this paper.

Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO 3 ) with Canavalia ensiformis lectin (Con A) and glycogen. MRP mean particle diameter and zeta potential were 857.8 ± 93.1 nm and 2.37 ± 4.12 mV, respectively. Tenofovir (TFV) encapsulation and loading efficiencies in MRP were 70.1% and 16.3% w/w, respectively. When exposed to HIV-1 rgp120 (25 μg/mL), MRP released a significant amount of TFV (∼5-fold higher) in vaginal and seminal fluid mixture compared to the control (pre-exposure) level (∼59 μg/mL) in vaginal fluid alone. Unlike the positive control treated groups (e.g., nonoxynol-9), no significant histological damages and CD45+ cells infiltration were observed in the vaginal and major reproductive organ epithelial layers. This was probably due to MRP biocompatibility and its isosmolality (304.33 ± 0.58 mOsm/kg). Furthermore, compared to negative controls, there was no statistically significant increase in pro-inflammatory cytokines such as IL1α, Ilβ, IL7, IP10, and TNFα. Collectively, these data suggest that MRP is a relatively safe nanotemplate for HIV-1 gp120 stimuli responsive vaginal microbicide delivery system.