OA26.04
Background: Multipurpose drug delivery systems (MDDS) have the potential to impart a variety of attributes to microbicide delivery. We have previously developed a safe and effective microbicide, using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that encapsulate short interfering (siRNA) targeting host receptors, to significantly increase survival in a murine model of HSV-2 infection; and have more recently developed surface-modified NPs that enhance cell internalization by 70%. Building upon these abilities in our new lab, we seek to create a proof-of-concept MDDS that integrates some of the protective attributes of mucus, including structure and pathogen adhesion, to target the integral stages of HIV-1 and HSV-2 infection. To achieve this, our MDDS incorporates 3 components:
(1) a biological lectin, Griffithsin (GRFT), to immobilize and debilitate HSV-2 and HIV upon entry (“trapping”); and “safety nets” of:
(2) polymeric electrospun fibers (EFs) and
(3) NPs to provide prolonged release of encapsulated antiviral drugs and siRNA, respectively.
Methods: EFs were electrospun with different solvents and compositions, containing our model small molecule antiviral, Acyclovir (ACV). A portion of EFs were surface modified with our “trapping” lectin, GRFT. Virus assays were conducted to test the efficacy of ACV EFs and blank GRFT-EFs against HSV-2 infection in vitro.
Results: EFs with a range of diameters were produced, depending on solvent selection and electrospinning conditions. We achieved high ACV encapsulation, with cumulative release spanning 20–60%. EFs encapsulating ACV inhibited HSV-2 infection by >90%, while GRFT-EFs immobilized HSV-2. We are currently expanding this platform to inhibit both HSV-2 and HIV infection.
Conclusions: We have complemented our siRNA NP and surface-modified NP microbicide platform, to create novel unmodified and GRFT-EFs for use in a MDDS. We are excited to further develop and combine these technologies to eventually capture, prevent, and treat STIs in one platform.
