Enhanced Targeting, Retention, and Penetration of Amphotericin B Through a Biomimetic Strategy to Treat Against Vulvovaginal Candidiasis

Abstract

An effective therapeutic strategy to treat vulvovaginal candidiasis (VVC) that is mainly caused by Candida albicans (C. albicans) infection is highly desirable. While Amphotericin B (AmB) has demonstrated promise, its precise localization to C. albicans burden at vaginal sites is oftentimes limited by the high fluidity microenvironment of the vagina, which can compromise treatment efficacy. To overcome this issue, a biomimetic AmB delivery system is developed, in which AmB preloaded polymeric cores are cloaked with vaginal epithelial cells membrane (VM‐ANP). With its cell membrane coating, VM‐ANP naturally targets and strongly binds with C. albicans, thus resisting the self‐cleaning of vaginal fluid. Besides its long retention property, VM‐ANP could penetrate deeply in vaginal tissue to achieve its full antifungal potential by attaching to hidden C. albicans. It is shown that both C. albicans suspension and biofilm biomass could be effectively inhibited by the VM‐ANP in vitro. In a C. albicans intravaginal infection model, treatment with VM‐ANP results in significantly decreased fungal challenges both in vaginal tissue and fluid. Overall, such biomimetic strategy adds the merit of natural cell membrane into the targeted delivery of drug in treating VVC, which also serves as a promising platform against vaginitis‐related pathogens.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a “Three-in-One” Strategy to Treat against Intravaginal Infection of Candida albicans

“…In order to fabricate the biomimetic nanoplatform VM(IR780)-PFC(O 2 ), the vaginal epithelial cell membrane (VM) was first collected according to the previous protocol. 21 To wrap the PFC with the VM, various volume/protein weight ratios of PFC/VM (μL/mg) were premixed together to a fixed final volume and then emulsified by a probe ultrasonicator. As the addition of the PFC increased, diameters of the formed VM-PFC nanoemulsions increased slightly as measured by dynamic light scattering (DLS) until the PFC/VM ratios were up to 25 μL/mg and beyond that resulting in a sharply increased size attributed to the uncoated PFC (Figure 1b).…”

“…In order to fabricate the biomimetic nanoplatform VM­(IR780)-PFC­(O 2 ), the vaginal epithelial cell membrane (VM) was first collected according to the previous protocol . To wrap the PFC with the VM, various volume/protein weight ratios of PFC/VM (μL/mg) were premixed together to a fixed final volume and then emulsified by a probe ultrasonicator.…”

“…By the VM dressing, VM­(IR780)-PFC­(O 2 ) was also expected to efficiently bind with C. albicans. Prior to testing the ability of VM­(IR780)-PFC­(O 2 ) to target C. albicans , we fabricated RM­(IR780)-PFC­(O 2 ) (employed a red blood cell membrane to coat PFC cores) as the control and characterized it (Supplementary Figure 3). After incubation with C. albicans , it was visualized by scanning electron microscopy (SEM) images that more accumulation of VM­(IR780)-PFC­(O 2 ) nanoparticles was covered onto the surface of C. albicans compared to that of RM­(IR780)-PFC­(O 2 ) (Figure e).…”

“…By translocating the parents’ cell plasma membrane, these biomimetic nanoparticles present a cell-like function of source cells. − For example, platelet membrane camouflaging endows nanoparticles with a targeting property for enhancing the delivery of antimicrobial agents to invasive microorganisms. , In another example, macrophage membrane-cloaked therapeutic nanoparticles can be effective at bactericidal ability via the specific adhesion to bacteria. , Also, the H. pylori bacteria-derived outer membrane vesicle coating adds its ability into nanoparticles to competitively block the specific receptors on the surface of gastric epithelial cells, resulting in decreased adhesion of H. pylori. Along this line, by inspiration from the natural binding capacity of C. albicans with the vaginal epithelium, we previously constructed a vaginal epithelial cell membrane (VM)-coated drug delivery system for C. albicans treatment . These nanoparticles with the VM dressing are capable of adhering to the surface of C. albicans and staying with each other all the time, while the unbound nanoparticles would be rapidly cleared away by vaginal fluid; thus, this C. albicans -biasing accumulation strategy provides a promising biomimetic nanoplatform for C. albicans -targeting treatment, particularly with the demand of precise phototherapy.…”

“…20 Along this line, by inspiration from the natural binding capacity of C. albicans with the vaginal epithelium, we previously constructed a vaginal epithelial cell membrane (VM)-coated drug delivery system for C. albicans treatment. 21 These nanoparticles with the VM dressing are capable of adhering to the surface of C. albicans and staying with each other all the time, while the unbound nanoparticles would be rapidly cleared away by vaginal fluid; thus, this C. albicansbiasing accumulation strategy provides a promising biomimetic nanoplatform for C. albicans-targeting treatment, particularly with the demand of precise phototherapy. While the enhanced targeting efficiency of phototherapeutic agents to C. albicans is a prerequisite, further improvement can still be made to improve the fungicidal efficacy, particularly for the design based on the specific factors during C. albicans infection.…”