Novel self-assembling conjugates as vectors for agrochemical delivery

(2018) 16:94 Nadiminti et al. J Nanobiotechnol https://doi.org/10.1186/s12951-018-0423-5 Journal of Nanobiotechnology Open Access RESEARCH Novel self‑assembling conjugates as vectors for agrochemical delivery Pavani P. Nadiminti1*†, Qingtao Liu2,3†, Lavanya K. Vanjari1, Yao D. Dong2, Ben J. Boyd2,3 and David M. Cahill1 Abstract Background: Modern agricultural practises rely on surfactant-based spray applications to eliminate weeds in crops. The wide spread and indiscriminate use of surfactants may result in a number of deleterious effects that are not limited to impacts on the crop and surrounding farm eco-system but include effects on human health. To provide a safer alternative to the use of surfactant-based formulations, we have synthesised a novel, self-assembling herbicide conjugate for the delivery of a broad leaf herbicide, picloram. Results: The synthesized self-assembling amphiphile–picloram (SAP) conjugate has three extending arms: a lipophilic lauryl chain, a hydrophilic polyethylene glycol chain and the amphiphobic agrochemical active picloram. We propose that the SAP conjugate maintains its colloidal stability by quickly transitioning between micellar and inverse micellar phases in hydrophilic and lipophilic environments respectively. The SAP conjugate provides the advantage of a phase structure that enables enhanced interaction with the hydrophobic epicuticular wax surface of the leaf. We have investigated the herbicidal efficiency of the SAP conjugate compared against that of commercial picloram formulations using the model plant Arabidopsis thaliana and found that when tested at agriculturally relevant doses between 0.58 and 11.70 mM a dose-dependent herbicidal effect with comparable kill rates was evident. Conclusion: Though self-assembling drug carriers are not new to the pharmaceutical industry their use for the delivery of agrochemicals shows great promise but is largely unexplored. We have shown that SAP may be used as an alternative to current surfactant-based agrochemical formulations and has the potential to shift present practises towards a more sustainable approach. Keywords: Self-assembly, Picloram, Herbicides, Arabidopsis thaliana, Surfactants, Weeds Background Common agricultural practises aimed at improving plant health and crop yield are heavily dependent on the use of surfactant-based agrochemical formulations. Such formulations are known for their off-target toxicity [1], lead to the over-use of chemicals [2] and may result in crop phytotoxicity [3, 4] ultimately resulting in yield loses. In addition, traditional agrochemicals may significantly contribute to pollution of the environment and can be deleterious to human health [5, 6]. To overcome these unintended impacts new strategies for agrochemical *Correspondence: † Pavani P. Nadiminti and Qingtao Liu contributed equally to the work 1 School of Life and Environmental Sciences, Deakin University, Waurn Ponds Campus, Geelong, VIC 3217, Australia Full list of author information is available at the end of the article delivery are under constant exploration [7, 8]. One such innovative strategy is the use of nanotechnology, which has opened new vistas for the delivery of agrochemicals to plants [9]. Unlike traditional agrochemicals, research with the model plant species, Arabidopsis thaliana, showed that mesoporous silica nanoparticles (MSNs), can deliver the phytohormone and disease resistance inducer, salicylic acid, in-planta only when redox stress is high [10]. Also, MSNs were shown to be able to deliver the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to control the growth of model weeds while simultaneously reducing soil contamination [11]. In our recent work, lyotropic liquid crystalline (LC) phases were shown in laboratory and field studies to minimise crop phytotoxicity while efficiently delivering 2,4-D to eliminate weeds [12]. LC systems have been shown to have high pharmaceutical value for their ability to deliver a range of molecules © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Nadiminti et al. J Nanobiotechnol (2018) 16:94 such as curcumin [13], chlorhexidine [14] and insulin [15]. LC systems encompass a number of phases such as lamellar phases, hexagonal phases and inverse bicontinuous cubic phases. The latter phases can simply be formed by dispersion in water of polar lipids such as phytantriol, glyceryl monooleate and glyceryl monoelaidin in the presence of a stabiliser [16]. Such LC systems have recently been of interest also for the delivery of agrochemical actives to plants. LC systems in inverse bicontinuous cubic phase structure can interact with hydrophobic plant surfaces, prevent crop phytotoxicity and reduce off target toxicity effects [12, 17]. In field trials the practical use of a surfactant free LC system for the delivery of 2,4-D to kill wild radish (Raphanus raphanistrum) in a wheat (Triticum aestivum) crop was demonstrated [17]. However, their success was dependent on the amphiphobic agrochemical in use that often hampers the stability of the formulation [18–20]. Agrochemical industries employ several strategies to improve the stability of oil in water emulsions, for example, by encapsulation of the active ingredient [21], alkoxylation of the hydrophobic active ingredient [22] and the use of solid dispersing agents to stabilise the emulsion containing lipophilic actives [23]. In a recent report we demonstrated the use of an agrochemical conjugate for the formation of a stable self-assembling LC carrier system [8]. The linear-picloram conjugate was prepared by covalently bonding agrochemical actives such as picloram or 2,4-D to a lipid, which, when exposed to water in the presence of a pluronic stabiliser, formed a self-assembling LC system. The use of such formulation is restricted by the presence of amphiphobic actives that limit their encapsulation into the LC system and reduces the colloidal stability of the formulation [8]. The disadvantages of such systems presents us with the need for the development of an ecologically safe, self-assembling agrochemical formulation that can not only form a stable carrier emulsion but also can efficiently deliver the active to target plants. The use of self-assembling liquid crystalline materials for the delivery of pharmaceutical actives is well described but has never been explored for the delivery of agrochemical actives [24]. We therefore, synthesized a nove (...truncated)