Intravaginal poly-(D, L-lactic-co-glycolic acid)-(polyethylene glycol) drug-delivery nanoparticles induce pro-inflammatory responses with Candida albicans infection in a mouse model

Abstract

In a recent study, using an in vitro model to study intravaginal nanoparticle exposure during yeast infections, we demonstrated that C . albicans exposure suppressed apoptotic gene expression and induced oxidative stress and pyroptosis in vaginal epithelial cells. The mucous-penetrating drug delivery nanoparticles made from poly-(D, L-lactic- co -glycolic acid)-(polyethylene glycol) induced cytotoxicity by activating apoptosis, endoplasmic reticulum (ER) stress, oxidative stress, and DNA damage repair responses alone and, in some cases with C . albicans . In the current study we evaluated the effects of fluorescently-labelled nanoparticles in CBA/J mice challenged intravaginally for two hours followed by intravaginal challenge with C . albicans for 18 hours. Nanoparticle treatment increased systemic translocation of C . albicans threefold in the heart. C . albicans also increased systemic distribution of the nanoparticles fivefold in the heart. Flow cytometric assays showed co-localization of the nanoparticles with epithelial cells, macrophages and dendritic cells. Nanoparticle-treated, C . albicans -infected mice exhibited induction of autophagy, ER stress, apoptosis, and inflammatory serum cytokines. C . albicans infection was associated with pyroptosis and suppressed expression of ER stress and apoptosis-related genes. Induction of apoptosis during nanoparticle treatment and in nanoparticle-treated- C . albicans infected mice was observed as DNA damage responses, mitochondrial depolarization and (Poly [ADP-Ribose] Polymerase) cleavage. C . albicans infection was associated with increased mRNA expression of anti-apoptotic genes. Both C . albicans infection and nanoparticle treatment showed enhanced chemoattraction of dendritic cells and polymorphonuclear cells to factors in vaginal washings in a chemotaxis assay. This study shows that both intravaginal treatment of mice with the nanoparticles and infection with C . albicans induce cytotoxic and inflammatory responses. C . albicans also suppressed cell apoptosis. These results clarify our understanding of how nanoparticles modulate host cellular responses during C . albicans infection and will be applicable for future research and development of intravaginal nanomedicines.

Copper-Nanoparticle-Induced Neurotoxic Effect and Oxidative Stress in the Early Developmental Stage of Zebrafish (Danio rerio)

“…The results indicated that the mRNA expression of inflammatory factors was regulated by CuNPs and CuCl 2 exposure ( Figure 9 ). Proinflammatory cytokines like IL-1β, IL-6, and TNF-α are commonly assessed to estimate the immunotoxicity of nanomaterials [ 57 ]. Changes in the mRNA expression of these cytokines in the present study provided evidence of immunotoxicity associated with CuNPs and CuCl 2 exposure.…”

Nanoparticles for Antimicrobial Agents Delivery—An Up-to-Date Review

“…Nanodimensional materials, such as metallic NPs, metal-oxide NPs, lipid-based NPs, and polymeric NPs, have attracted considerable interest in recent years for fabricating delivery vehicles. Specifically, the variety and versatility of nanomaterials have been extensively explored by researchers for creating innovative therapeutic formulations that can be administrated on different routes, including oral [2,141,142], ocular [82,83,143], intranasal [125,129,130], intratracheal [55,144], intravaginal [145,146], intravesical [147,148], and transdermal [149,150] routes. Compared to free drugs, NP-loaded antimicrobial agents can be administered in so many ways due to their increased safety, reduced systemic adverse effects, enhanced solubility, and improved bioavailability.…”