Next Article in Journal / Special Issue
In Situ-Based Gels for Nose to Brain Delivery for the Treatment of Neurological Diseases
Previous Article in Journal / Special Issue
Chitosan Glutamate-Coated Niosomes: A Proposal for Nose-to-Brain Delivery
Article Menu

Export Article

Open AccessReview
Pharmaceutics 2018, 10(2), 39; https://doi.org/10.3390/pharmaceutics10020039

Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?

1
Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy
2
Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy
*
Author to whom correspondence should be addressed.
Received: 21 February 2018 / Revised: 16 March 2018 / Accepted: 19 March 2018 / Published: 26 March 2018
(This article belongs to the Special Issue Nose to Brain Delivery)
View Full-Text   |   Download PDF [341 KB, uploaded 3 May 2018]   |  

Abstract

Although several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1), multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5), and breast cancer resistance protein (ABCG2 or BCRP). Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions), absorption enhancers (chitosan, papaverine), and mucoadhesive agents (chitosan, polyvinilpyrrolidone) are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV) agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body. View Full-Text
Keywords: active efflux transporter; antiretroviral drug; HIV sanctuaries; thermoreversible gel; nano-emulsion; polymeric microparticles; polymeric nanoparticles; nasal formulation; solid lipid microparticles; virus active efflux transporter; antiretroviral drug; HIV sanctuaries; thermoreversible gel; nano-emulsion; polymeric microparticles; polymeric nanoparticles; nasal formulation; solid lipid microparticles; virus
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Dalpiaz, A.; Pavan, B. Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux? Pharmaceutics 2018, 10, 39.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top