Green Solvents Made From Natural Ingredients Could Transform Drug Delivery

A new review published in the Journal of Nanoparticle Research argues that a family of solvents borrowed directly from living cells could solve some of the most stubborn problems in modern drug delivery. Narendra Bajirao Patil of the H. R. Patel Institute of Pharmaceutical Education and Research in India and Subash C. B. Gopinath, affiliated with Saveetha Medical College and Hospital, Dogus University and Universiti Malaysia Perlis, survey the rapidly growing field of natural deep eutectic solvents, or NADES, and their integration into nanoscale drug carriers. Their assessment, published on 29 August 2026 as volume 28, article 233 of the journal, positions these liquids as a sustainable foundation for the next generation of pharmaceutical formulations.

Natural deep eutectic solvents occupy a curious place in chemistry. They arise when certain natural compounds, typically a hydrogen bond donor and a hydrogen bond acceptor such as an amino acid, a sugar, an organic acid or choline chloride, are mixed in specific ratios. The resulting mixture behaves in a striking way: instead of crystallizing as its individual components would, it melts or remains liquid at temperatures far lower than either ingredient alone, forming a stable eutectic liquid. The concept gained prominence in 2011, when researchers proposed in Plant Physiology that such mixtures might be the missing link in understanding cellular metabolism, since cells are crowded with exactly these kinds of small molecules. By 2013, Dai and colleagues had framed NADES as a new potential medium for green technology, and the field has expanded steadily since.

What makes NADES attractive to pharmaceutical scientists is the combination of properties they bring to the table. They are largely non-toxic, biodegradable and inexpensive to produce, often from food-grade or metabolite-grade starting materials. They can be synthesized sustainably by several methods, and their characteristics can be tuned, for example by adjusting water content, which alters viscosity and other physicochemical parameters. Studies have shown that adding water tailors NADES properties to facilitate applications, and that these solvents even modulate the thermal behavior of water, which has led to their exploration as non-toxic cryoprotective agents. Crucially for drug delivery, NADES excel at dissolving poorly water-soluble molecules, a chronic bottleneck, since a large fraction of active pharmaceutical ingredients and phytochemicals exhibit solubility so low that oral absorption becomes unreliable.

The review’s central argument is that pairing NADES with nanocarriers multiplies these advantages. Conventional drug delivery systems face a familiar litany of shortcomings: lack of targeted delivery, fluctuation in drug release, possible side effects, frequent dosing requirements, environmental hazards and high costs. Nanocarrier-based delivery already offers substantial rewards over conventional systems, but the carriers themselves often rely on solvents and excipients that raise toxicity or environmental concerns. The authors highlight, for instance, pro-inflammatory concerns that have been raised with lipid nanoparticles, the platform behind mRNA vaccines, and safety questions surrounding these systems for nucleic acid delivery. NADES-integrated nanocarriers, by contrast, promise low toxicity, biodegradability, cost-effectiveness and tunability, while enhancing the therapeutic efficacy of bioactive drugs.

The technical landscape covered in the review is broad. Solid lipid nanoparticles and nanostructured lipid carriers, established platforms for improving bioavailability and enabling targeted therapy, have been combined with NADES to encapsulate compounds such as curcumin, a notoriously insoluble but biologically active polyphenol. One 2024 study reported enhanced curcumin delivery and stability through NADES-based niosomes, vesicular carriers assembled from non-ionic surfactants. Another line of work integrated natural deep eutectic solvents into nanostructured lipid carriers with an explicitly industrial outlook, and a 2025 study used green nanostructured lipid carriers and NADES to solubilize extracts from Brazilian Cerrado byproducts, boosting antioxidant potential and simultaneously valorizing agricultural waste. Thermosensitive niosomes have even been designed from eutectic mixtures of natural fatty acids, adding stimulus-responsive behavior to the toolkit.

Polymeric systems feature prominently as well. Researchers have synthesized biodegradable poly(2-hydroxyethyl methacrylate) using NADES for sustainable cancer drug delivery, and fabricated green poly(vinyl alcohol) nanofibers with NADES for fast-dissolving drug delivery. Doxorubicin, a mainstay chemotherapy agent, has been loaded onto functional graphene nanocarriers using ternary deep eutectic solvent systems. A targeted solid-liquid polymer carrier supported by NADES has been explored for breast cancer therapy. Beyond polymers, the review describes NADES-based surfactant-free microemulsions that solubilize and extract curcumin from turmeric, and eutectogels, gel networks formed within deep eutectic solvents, that have been engineered for colon-targeted delivery of mesalazine, an anti-inflammatory drug used in inflammatory bowel disease. Smart supramolecular eutectogels have been designed for pH- and thermo-responsive transdermal delivery of anticancer curcumin, illustrating how the platform can incorporate environmental triggers.

The application domains extend well beyond cancer. In wound care, a curcumin emulgel enriched with a camphor-menthol-based deep eutectic solvent demonstrated wound healing efficacy, and NADES-based chitosan hydrogels have been developed for enhanced photoimmunomodulation treatment of various wounds. Nano-electrospun membranes combining NADES with Platostoma palustre polysaccharides and polyvinyl alcohol showed transdermal properties and bioactivity. In dermatology, a deep eutectic solvent-assisted kaempferol hydrogel emerged as a promising therapeutic approach for psoriasis-like skin inflammation. Ocular medicine has joined in too: green-sourced polyphenols delivered through a sustainable NADES-based approach have been proposed for dry eye disease treatment. Cosmeceutical applications include the green extraction of Rosa canina and Prunus spinosa by NADES followed by encapsulation in chitosan nanoparticles, and deep eutectic solvent nanoparticles have been used to enhance intradermal delivery of hyaluronic acid for anti-aging and moisturizing effects.

The mechanisms underlying these systems are as varied as the formulations. NADES can act as solubilizing media within the carrier, as structural components of the carrier itself, or as permeation enhancers that interact with biological membranes. Research into how NADES interact with artificial and natural membranes supports their role in facilitating transport across the skin and mucosal barriers. Choline chloride-malic acid NADES containing hydrophobic drugs has been studied for solubility and permeability behavior in digestive tract models, informing oral delivery design. Methotrexate solubilization and transdermal delivery have been enhanced in microemulsions with NADES screened by computational COSMO-RS methods, showing how molecular simulation can guide solvent selection. Pharmacokinetic evidence is accumulating as well: rutin dissolved in a proline-glycine NADES showed improved bioavailability after oral administration in rats, and deep eutectic solvents altered the pharmacokinetics of salvianolic acid B in rats, with acute toxicity testing performed alongside. Notably, NADES have also been shown to protect RNA from thermal degradation, and a ready-to-use lipid nanoparticle technology for nucleic acid delivery based on deep eutectic solvents has been developed, hinting at relevance for gene therapy and mRNA medicine.

Safety data, while still maturing, are encouraging. Cytotoxicity profiling of choline chloride-based NADES has been carried out, and toxicity studies of a betaine-glycerol NADES in rats have been published. A noncytotoxic, hemocompatible ion gel was prepared by self-polymerization of 2-hydroxyethyl methacrylate in a green deep eutectic solvent, and hydrogel formulations containing lidocaine have incorporated NADES to advantage. Buccal xanthan gum-hyaluronic acid eutectogels with dual anti-inflammatory and antimicrobial properties have been reported, relevant given the well-documented organ damage and gastrointestinal risks associated with long-term nonsteroidal anti-inflammatory drug use. Alginate hydrogels incorporating essential oils loaded in chitosan nanoparticles extend the platform to biomedical applications such as antimicrobial wound management.

The review is candid about the obstacles standing between laboratory promise and clinical reality. Viscosity, limited recyclability and safety data, long-term stability and scalability remain key issues for large-scale industrial application. High viscosity complicates handling, mixing and manufacturing; the recyclability of these solvents at industrial scale is not yet established; and comprehensive long-term safety and stability profiles are still being assembled. Regulatory pathways for such novel combination products also require clarification, a theme echoed in broader discussions of nanopharmaceutical quality-by-design frameworks and post-marketing surveillance. The authors frame their work as identifying these challenges, research gaps and opportunities for translating NADES-based nanocarrier technologies from laboratory scale to clinical and industrial application, and as a theoretical foundation for broader use in pharmaceutical and biomedical fields. If those gaps close, the vision is compelling: drug carriers built from the same molecular vocabulary that cells themselves use, delivering difficult medicines more safely, more sustainably and more effectively.

Subject of Research: Natural deep eutectic solvent-based nanocarriers for sustainable drug delivery

Article Title: Engineering green nanocarriers using natural deep eutectic solvents: a sustainable platform for modern drug delivery

Article References: Patil, N. B., & Gopinath, S. C. B. (2026). Engineering green nanocarriers using natural deep eutectic solvents: a sustainable platform for modern drug delivery. Journal of Nanoparticle Research, 28(9), Article 233. https://doi.org/10.1007/s11051-026-06749-0

Image Credits: AI Generated

DOI: 10.1007/s11051-026-06749-0

Keywords: natural deep eutectic solvents, NADES, nanocarriers, drug delivery, green chemistry, lipid nanoparticles, niosomes, eutectogels, curcumin, biomedicine, pharmaceuticals, sustainability