Continuous drug release by sea anemone Nematostella vectensis stinging microcapsules.

Yossi Tal,Vera Brekhman,Ari Ayalon,Agnesa Sharaev,Tamar Lotan,Zoya Kazir

doi:10.3390/md12020734

Abstract

Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery.

Highlights

The phylum Cnidaria, comprising sea anemones, corals, jellyfish and hydra, is one of the most ancient extant multicellular phyla, dating back about 700 million years [1]
We have previously demonstrated that the ultra-fast characteristic of the nematocysts can be leveraged to develop a natural microinjection system for immediate transdermal drug delivery with the microcapsular shell serving as the syringe barrel, the tubule as the syringe needle, and poly-γ-glutamate aggregate as the plunger
The aim of this work was to investigate the potential use of the N. vectensis nematocyst system as a vehicle for continuous transdermal drug delivery

Summary

Introduction

The phylum Cnidaria, comprising sea anemones, corals, jellyfish and hydra, is one of the most ancient extant multicellular phyla, dating back about 700 million years [1]. Water flowing through the porous net wall of the activated microcapsule causes the aggregated poly-γ-glutamate to dissociate. This in turn increases the osmotic pressure to 150 bars, resulting in ejection of the tubule and continuous injection of the microcapsular contents until the poly-γ-glutamate is fully swept out of the microcapsule [4]. The system was tested using microcapsules isolated from the sea anemone Aiptasia diaphana [7,8,9]

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Conclusion