Novel ex vivo protocol using porcine vagina to assess drug permeation from mucoadhesive and colloidal pharmaceutical systems

Pereira, Maíra N.; Reis, Thaiene Avila; Matos, Breno N.; Cunha-Filho, Marcílio; Gratieri, Taís

doi:10.1016/j.colsurfb.2017.07.008

Cited by 18 publications

(8 citation statements)

References 18 publications

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“…A new ex vivo protocol developed by Pereira et al used porcine vagina in a vertical permeation model to evaluate the absorption of ketoconazole nanoparticles. Care for the preservation of all structures of the organ was duly taken, with it being suspended in a position similar to the anatomical position.…”

Section: Alternative Methods That Simulate Fungal Infectionsmentioning

confidence: 99%

Fungal infection models: Current progress ofex vivomethods

Quatrin

Lana

Kaminski

2019

Mycoses

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| INTRODUC TI ONThe principles developed by Russell and Burch in 1959, concerning the use of animals in research, have been updated in recent decades, and cover the use of tissues from dead animals as alternatives to in vivo methods. 1 In vivo tests generally involve a large number of specimens to obtain representative results, and the well-being of these animals has become an ethical issue to be respected. 2 The term ex vivo refers to the use of living tissues, which are removed from an organism in vivo, for the application in experiments that will be performed in an artificial environment. 3The murine models used to evaluate the therapeutic profile of new antifungal agents are addressed in several studies, such as induction of keratitis, onychomycosis, and systemic, vaginal, pulmonary and cutaneous infections. 4-9 However, it is important to maintain a balance between qualified science and animal well-being, using rational and ethical ways of research. In this scenario, ex vivo models that simulate fungal infections in nails, mucous membranes and skin are promising alternatives that have been showing considerable results. [10][11][12] In order to demonstrate new perspectives in the evaluation of antifungal therapy, we will approach a critical review of the main ex vivo techniques used in the simulation and treatment of mycoses, providing an adaptation of the widely used in vivo methods. | ME THODS | Data source SummaryExperimental alternative ex vivo models that simulate infectious processes in vivo are of fundamental importance for the evaluation of new drugs, since in some cases, their execution does not depend on the approval of an ethics committee in research.Although studies using alternative infectious models to evaluate the efficacy of antifungal molecules have been increasingly described and reported, there is no critical consensus that establishes the most appropriate ones regarding the type of infection. Numerous studies contemplate ex vivo protocols of fungal infections on nails, corneas, dentinal tubules and skin and reveal counterpoints and concordances not yet finely confronted. In this minireview, we propose a critical analysis of the main ex vivo models of fungal infections for the evaluation of new antifungal candidates for both topical and systemic use, as opposed to the advantages and disadvantages of the traditional in vivo models employed in preclinical research. K E Y W O R D S dentinal tubule infections, ex vivo models, mucosal infections, onychomycosis, skin infection, systemic infections | 861 MACIEL QUATRIN ET AL. How to cite this article: Maciel Quatrin P, Flores Dalla Lana D, Andrzejewski Kaminski TF, Meneghello Fuentefria A. Fungal infection models: Current progress of ex vivo methods.

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Section: Alternative Methods That Simulate Fungal Infectionsmentioning

confidence: 99%

Fungal infection models: Current progress ofex vivomethods

Quatrin

Lana

Kaminski

2019

Mycoses

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“…By integrating some of the attributes of in vitro and in vivo systems, ex vivo models can provide physiologically relevant tissue architectures, representative of the FRT microenvironment. In particular, porcine vaginal tissue has been used to investigate the mucoadhesive properties of NPs and other colloidal systems, as described in the studies by Pereira et al 41 and van Eyk and van der Bijl. 86 Similar methodologies have been used to investigate the efficacy of tenofovir-encapsulated chitosan NPs as a potential microbicide.…”

Section: Toward More Realistic In Vitro Systemsmentioning

confidence: 99%

“…Moreover, alterations in physicochemical properties can be adapted to attain desired pharmacokinetic (PK) and pharmacodynamic (PD) properties. 6,7,10,14,15,19,23,26,27,36,39,41 Thus, polymeric NPs can be designed to overcome transport barriers and to deliver effective doses to target sites, while maintaining agent activity and minimizing adverse effects on surrounding tissue.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-mediated drug delivery to treat infections in the female reproductive tract: evaluation of experimental systems and the potential for mathematical modeling

Sims¹,

Frieboes²,

Steinbach-Rankins³

2018

IJN

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A variety of drug-delivery platforms have been employed to deliver therapeutic agents across cervicovaginal mucus (CVM) and the vaginal mucosa, offering the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract (FRT). Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, polymeric NPs represent a promising option that has shown improved distribution through the CVM. These NPs are typically fabricated from nontoxic, non-inflammatory, US Food and Drug Administration-approved polymers that improve biocompatibility. This review summarizes recent experimental studies that have evaluated NP transport in the FRT, and highlights research areas that more thoroughly and efficiently inform polymeric NP design, including mathematical modeling. An overview of the in vitro, ex vivo, and in vivo NP studies conducted to date – whereby transport parameters are determined, extrapolated, and validated – is presented first. The impact of different NP design features on transport through the FRT is summarized, and gaps that exist due to the limitations of iterative experimentation alone are identified. The potential of mathematical modeling to complement the characterization and evaluation of diffusion and transport of delivery vehicles and active agents through the CVM and mucosa is discussed. Lastly, potential advancements combining experimental and mathematical knowledge are suggested to inform next-generation NP designs, such that infections in the FRT may be more effectively treated.

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“…Moreover, alterations in physicochemical properties can be adapted to attain desired pharmacokinetic (PK) and pharmacodynamic (PD) properties. 1,2,8,9,12,16,17,21,25,36,39,41 Thus, polymeric NPs can be designed to overcome transport barriers and to deliver effective doses to target sites, while maintaining agent activity and minimizing adverse effects on surrounding tissue.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Section: Ex Vivo Transport Studiesmentioning

confidence: 99%

PLGA-modified nanoparticles for the treatment of hypo-vascularized HPV-related cervical cancers.

Sims¹

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(CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, polymeric NPs represent a promising option that has shown improved distribution through the CVM. This work summarizes recent experimental studies that have evaluated NP transport in the FRT, and highlights research areas that more thoroughly and efficiently inform polymeric NP design, including mathematical modeling. The studies presented below further expand on this to investigate the application of NPs in treating cancers found within the FRT. Advanced stage cancer treatments are often invasive and painful-typically comprised of surgery, chemotherapy, and/or radiation treatment. In addition to the poor transport associated with intravaginal delivery, low transport efficiency during systemic chemotherapy may require high chemotherapeutic doses to effectively target cancerous tissue, resulting in systemic toxicity. Nanotherapeutic platforms have been proposed as an alternative to more safely and effectively deliver therapeutic agents directly to tumor sites. However, cellular internalization and tumor penetration are often diametrically opposed, with limited access to tumor regions distal from vasculature, due to irregular tissue morphologies. To address these transport challenges, NPs are often surface-modified with ligands to enhance transport and longevity after localized or systemic administration. In the work presented below, the effect of surface modification with stealth polyethylene-glycol (PEG), cell-penetrating (MPG), and CPP-stealth (MPG/PEG) poly(lactic-co-glycolic-acid) (PLGA) NP co-treatment strategies on NP distribution and chemotherapeutic efficacy, which is defined in this work as the vi ability of NPs to impart drug cytotoxicity and potency, was evaluated with the use of 3D cell culture models representing hypo-vascularized cervical cancerous tissue.

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Novel ex vivo protocol using porcine vagina to assess drug permeation from mucoadhesive and colloidal pharmaceutical systems

Cited by 18 publications

References 18 publications

Fungal infection models: Current progress ofex vivomethods

Fungal infection models: Current progress ofex vivomethods

Nanoparticle-mediated drug delivery to treat infections in the female reproductive tract: evaluation of experimental systems and the potential for mathematical modeling

PLGA-modified nanoparticles for the treatment of hypo-vascularized HPV-related cervical cancers.

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