The Evaluation of Bac7 Labeled Nanocarriers to Deliver Antiretrovirals as a Pre‐Exposure Prophylaxis (PrEP) Therapy for HIV Prevention

Abstract

ObjectiveThe objective of this study is to engineer nanocarriers (NCs) capable of translocating through colorectal mucus and tissue and delivering drugs into cells of the distal colon. NCs will be delivered in quickbreak foams to provide sufficient colorectal coverage and be used as a colorectal PrEP therapy to prevent HIV transmission.MethodsFITC‐labeled poly(ethylene glycol) NCs were conjugated to the protease inhibitor amprenavir (APF) or cell‐penetrating peptide (CPP) Bac7 (BPF). APF and BPF were used to treat Caco‐2 cells in vitro and cell uptake was studied via flow cytometry. Mice were also treated with enemas containing APF or BPF and tissue retention was investigated. Foam formulations were studied for their ability to distribute NCs evenly throughout the distal colon. Histology and toxicity studies were also completed to assess the safety of the foam formulation.ResultsBPF uptake was shown to be 4‐fold higher than APF in vitro. Similar results were seen in vivo and BPF was retained within colorectal tissue for up to 5 days suggesting transport into the lamina propria. Ex vivo tissue samples show complete coverage of the distal colon by foams and NCs. Preliminary toxicity data of foam components display promising results based on histological observations.ConclusionBac7 CPP increased the translocation of NCs across the colorectal mucus and increased uptake into colonic cells both in vitro and in vivo. The current foam formulation is effective in providing uniform coverage of the distal colon and causes minimal tissue damage.AcknowledgementsFunding by NIH Grants T32GM8339, 1R01AI084137 and R37AI/DK‐051214