Iontophoresis for the cutaneous delivery of nanoentraped drugs

ABSTRACT

Introduction

The skin is an attractive route for drug delivery. However, the stratum corneum is a critical limiting barrier for drug permeation. Nanoentrapment is a way to enhance cutaneous drug delivery, by diverse mechanisms, with a notable trend of nanoparticles accumulating into the hair follicles when topically applied. Iontophoresis is yet another way of increasing drug transport by applying a mild electrical field that preferentially passes through the hair follicles, for being the pathway of lower resistance. So, iontophoresis application to nanocarriers could further increase actives accumulation into the hair follicles, impacting cutaneous drug delivery.

Areas covered

In this review, the authors aimed to discuss the main factors impacting iontophoretic skin transport when combining nanocarriers with iontophoresis. We further provide an overview of the conditions in which this combination has been studied, the characteristics of nanosystems employed, and hypothesize why the association has succeeded or failed to enhance drug permeation.

Expert opinion

Nanocarriers and iontophoresis association can be promising to enhance cutaneous drug delivery. For better results, the electroosmotic contribution to the iontophoretic transport, mainly of negatively charged nanocarriers, charge density, formulation pH, and skin models should be considered. Moreover, the transfollicular pathway should be considered, especially when designing the nanocarriers.

KEYWORDS:

• Nanocarriers
• nanoparticles
• skin
• transdermal drug delivery
• trans-follicular route

Article highlights

• Iontophoresis is presented in the context of cutaneous drug delivery.

• Positive outcomes have been related to the association between nanocarriers and iontophoretic.

• Positively charged nanocarriers may result in higher transdermal drug delivery enhancement in physiological pH.

• Electroosmotic contribution is often neglected in the iontophoretic transport of negatively charged nanocarriers.

• Strategies to increase the charge density of nanocarriers provide better results with iontophoresis.

• Hair follicles are an important yet overlooked penetration pathway for nanocarriers under iontophoresis.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the Brazilian funding agency CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, Grant n. 402587/2021-9), the Federal District Research Support Foundation (FAP-DF, Brazil, Grant n. 00193-00000802/2021-04), and the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil).