Abstract

Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using MethocelTM K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use.

Highlights

  • In the formulation based on DELOS nanovesicles integrating recombinant human Epidermal Growth Factor (rhEGF), cetyltrimethylammonium bromide (CTAB)

  • DELOS nanovesicles composed of two types of quaternary ammonium surfactants, CTAB and cetyltrimethylammonium chloride (CTAC), which differ in the counterion used—bromide and chloride, respectively—were prepared by the eco-efficient one-step DELOS-SUSP methodology

  • Media such as water; acetate buffer, pH = 5.0; histidine buffer, pH = 7.0; and phosphate-buffered saline (PBS) buffer, pH = 7.4, were used for DELOS nanovesicles production, yielding dispersions with excellent physicochemical properties. These liquid dispersions were gellified for the first time by adding 2% w/w MethocelTM K4M obtaining DELOS nanovesicles-based hydrogels with good macroscopic appearance and appropriate rheological properties for the intended use

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Summary

Introduction

Research on nanomedicine is making a revolution all over the world to offer more innovative and enhanced strategies of diagnosis and treatment compared with the conventional ones. In this frame, plenty of nanomedicines exist nowadays [1], the translation of a promising nanoformulation from the laboratory to the market is usually challenging and may take several years to reach its final commercialization. One of the tough challenges in this domain is to ensure the maximum quality, efficacy, and security of the drug product in the chosen administration route [2]. Among the different drug administration routes, it is of great interest to highlight that topical delivery presents several advantages since the skin is considered the most

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