Nanoparticle Transport from Mouse Vagina to Adjacent Lymph Nodes

Ballou, Byron; Andreko, Susan; Osuna-Highley, Elvira; McRaven, Michael D.; Catalone, Tina; Bruchez, Marcel P.; Hope, Thomas J.; Labib, Mohamed E.

doi:10.1371/journal.pone.0051995

Cited by 23 publications

(23 citation statements)

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“…Previously after intravaginal instillation PLGA NPs were taken up by the vaginal epithelium cells, accumulated in the sub epithelial stroma of the vagina (Cu et al, 2011). Moreover, quantum dots entered the draining lymph nodes after 36 h from intravaginal instillation (Ballou et al, 2012). Our data introduce a step forward for these previous studies, i.e.…”

Section: Discussionmentioning

confidence: 60%

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Histopathological and immunological changes induced by magnetite nanoparticles in the spleen, liver and genital tract of mice following intravaginal instillation

Awaad

2015

The Journal of Basic & Applied Zoology

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Recently, vaccination against sexually transmitted diseases as well as tumor therapy using new systems such as nanomaterials is a promising strategy. For successful usefulness of magnetite nanoparticles (MNPs) in medical applications through the vaginal route, it is essential to understand their biological fate and cellular toxicity in the animal tissues. This study aims to investigate the biodistribution, histopathological and immunological impacts of MNPs on in the liver, spleen and genital tract tissues of female mice after the intravaginal instillation. MNPs were observed within spleen and liver parenchyma as well as vaginal stroma after 3 days and 2 weeks of the instillation, and completely cleared from the vaginal stroma tissue after 6 weeks. Splenic lymphocytes of treated spleen were characterized with anisokaryosis; anisochromia. Quantitatively, the number of megakaryocyte and lymphocyte nuclei size in the spleen were highly increased after instillation of MNPs. MNPs caused acute inflammation in the liver and tarsal joints dermal. Immunologically, MNPs induced the vaginal secretion IgA and Bcl-2 reactivity in the hepatocytes, the expression of fucose residues and number of BM8 + cells in the genital tract tissues after instillation. Our data indicated that MNPs could influence the splenic lymphocytes and hepatocytes as well as the cellular and humoral immune responses in the mice genital tract tissues after 2 weeks of intravaginal instillation. This information could be useful for avoiding the side effects of MNPs

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Section: Discussionmentioning

confidence: 60%

“…Previous studies also did not reveal any detailed results about biodistribution and fate of MNPs after the intravaginal instillation. Previously, quantum dots and PLGA NPs were observed in the draining lymph nodes and female genital tract tissues after intravaginal instillation (Ballou et al, 2012;Cu et al, 2011).…”

Section: Introductionmentioning

confidence: 97%

Histopathological and immunological changes induced by magnetite nanoparticles in the spleen, liver and genital tract of mice following intravaginal instillation

Awaad

2015

The Journal of Basic & Applied Zoology

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“…Increased levels of IgG and IgA were found in vaginal fluid after intravaginal immunization compared to intranasal immunization, which resulted in increased resistance to vaginal HSV-2 infection [150]. Ballou et al investigated the transport of cadmium quantum dots (QD) (diameter not specified) from the vagina to adjacent lymph nodes [151]. They used quantum dots with various surface functionalization, including streptavidin QD (Sav), streptavidin QD functionalized with biotin-polyarginine (Sav-polyarg), carboylated QD (Carboxyl) and PEGylated QD.…”

Section: Dendrimersmentioning

confidence: 99%

Nanoparticle-based drug delivery to the vagina: A review

Ensign

Cone

Hanes

2014

Journal of Controlled Release

182

111

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Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted.

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“…A number of nanoparticle-based platforms, including polymeric nanoparticles, [6] and quantum dots, [7] have been developed that show potential in animal models for preventing sexually transmitted infections, [8] prophylaxis against the development of cervicovaginal tumors, [9] and improved siRNA delivery [10] . However, conventional polymeric nanoparticles, including those composed of polymers used in FDA-approved products, poly(lactic- co -glycolic acid) (PLGA) and polycaprolactone, are easily immobilized by the visocoelastic and adhesive cervicovaginal mucus (CVM) secretions coating the CV epithelium.…”

Section: Introductionmentioning

confidence: 99%

Vaginal Delivery of Paclitaxel via Nanoparticles with Non‐Mucoadhesive Surfaces Suppresses Cervical Tumor Growth

Yang

Wang

et al. 2013

Adv Healthcare Materials

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Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early stage cervical cancer. We hypothesize drug-loaded nanoparticles must rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract to effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner. We develop paclitaxel-loaded nanoparticles, composed entirely of polymers used in FDA-approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. We further employ a mouse model with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (conventional particles , or CP) and similar particles coated with Pluronic® F127 (mucus-penetrating particles , or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel-MPP suppress tumor growth more effectively and prolong median survival of mice compared to free paclitaxel or paclitaxel-CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel-MPP may be safe for intravaginal use. These results demonstrate for the first time the in vivo advantages of polymer-based MPP for treatment of tumors localized to a mucosal surface.

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Nanoparticle Transport from Mouse Vagina to Adjacent Lymph Nodes

Cited by 23 publications

References 50 publications

Histopathological and immunological changes induced by magnetite nanoparticles in the spleen, liver and genital tract of mice following intravaginal instillation

Histopathological and immunological changes induced by magnetite nanoparticles in the spleen, liver and genital tract of mice following intravaginal instillation

Nanoparticle-based drug delivery to the vagina: A review

Vaginal Delivery of Paclitaxel via Nanoparticles with Non‐Mucoadhesive Surfaces Suppresses Cervical Tumor Growth

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