Investigation of Nonionic Surfactant-Cyclodextrin Hydrogels for Hydrophobic Drug Delivery

Abstract

Supramolecular hydrogels have attracted increasing attention in drug delivery, tissue engineering, and injectable biomaterials because of their high water content, good biocompatibility, and dynamic network structures. Cyclodextrin-based supramolecular systems can form network structures through host–guest interactions. These systems usually require mild cross-linking conditions and allow flexible control of material properties, which gives them potential for biomedical applications. However, studies on the gelation behavior of different nonionic surfactant–cyclodextrin systems and their structure–property relationships are still limited.
In this study, six nonionic surfactants were selected, including the polysorbates 20 and polysorbate 80, and the alkyl glycosides α-dodecyl maltoside, β-dodecyl maltoside, decyl glucoside, and lauryl glucoside. These surfactants were mixed with α-cyclodextrin and β-cyclodextrin to investigate their gelation behavior and possible assembly mechanisms. The study first screened the phase behavior of the systems by changing the surfactant type, cyclodextrin type, water content, and molar ratio. The study further carried out rheological measurements, nuclear magnetic resonance analysis, injectability evaluation, and in vitro curcumin release experiments.
The results showed that different surfactants formed different assembly structures with cyclodextrins. Most alkyl glycoside systems showed phase separation or precipitation after centrifugation and failed to form stable hydrogels. The nuclear magnetic resonance results indicated that the strong host–guest interactions between α-cyclodextrin and dodecyl maltoside favored the formation of dense aggregates rather than continuous three-dimensional networks.
In contrast, the systems formed by Polysorbate 20 or Polysorbate 80 with α-cyclodextrin showed better stability. The systems formed stable hydrogels at higher α-cyclodextrin/Polysorbate 80 molar ratios and lower water contents. Rheological measurements showed that these hydrogels had clear viscoelastic behavior. The storage modulus remained higher than the loss modulus. The systems also showed obvious shear-thinning and thixotropic recovery behavior. These results indicated that the hydrogels possessed dynamic and reversible network structures together with good injectability.
The study also prepared curcumin-loaded systems using Polysorbate 80/α-cyclodextrin hydrogels as carriers. The results showed that the hydrogels could encapsulate curcumin–cyclodextrin inclusion complexes and provide sustained drug release. Different curcumin-cyclodextrin inclusion ratios influenced the release behavior. These findings suggested that the supramolecular structures and host–guest interactions inside the systems affected the drug diffusion process.

Popular Abstract

Although the human body contains 206 bones, it is by no means a rigid system. Approximately 60% of the human body consists of water, and the water content of many soft tissues is even higher. From a materials science perspective, the human body can therefore be regarded as a large, soft, naturally occurring hydrogel. This raises an important question: when diseases, injuries, or surgical procedures leave cavities and wounds within the body, what kind of material is most suitable for supporting tissue repair? The answer may not lie in rigid materials, but rather in a soft, water-rich, and even flowable gel.
In my research, I attempted to develop a novel hydrogel material capable of behaving both like a liquid and a solid. Ideally, it should be injectable like a liquid, allowing it to flow into deep wounds and irregular cavities, while subsequently recovering a jelly-like state after injection and remaining localized at the target site to support tissue repair. To achieve this goal, the capacity of six different nonionic surfactants to form gels together with cyclodextrin was investigated. Nonionic surfactants can be thought of as tiny molecular bridges between water and oil, two substances that normally do not mix. One end of the molecule prefers water, while the other prefers oil, allowing it to bring the two together. Because these molecules do not carry an electrical charge in water, they are known as nonionic surfactants. Four of these (alkyl glycosides) were initially expected to form stable gels; however, the experimental results were unsatisfactory. After high-speed centrifugation, these samples underwent phase separation and failed to maintain stable structures. In contrast, systems composed of Tween (polysorbate) 20 or Tween (polysorbate) 80 together with α-cyclodextrin exhibited markedly different and more promising behavior. Under specific compositional ratios, these systems behaved like elastic gels under static conditions, but temporarily flowed like liquids when subjected to stress, such as during injection through a syringe.
One of the most remarkable observations appeared during the later stages of the experiments. Immediately after preparation, the samples resembled ordinary liquids and flowed freely. However, after standing for a period of time, the material underwent a striking transition. When the glass vial was inverted, the sample remained firmly attached to the bottom without flowing downward, as though it had transformed into an elastic gel. This “solid-like at rest, liquid-like under stress” behavior directly corresponds to its potential biomedical applications. The material could first be injected into irregular cavities in a liquid-like state and subsequently reform into a soft gel capable of filling wounds and remaining localized at the treatment site.
More importantly, this hydrogel system may also serve as a carrier for poorly water-soluble drugs. In this way, therapeutic agents would no longer need to circulate extensively throughout the entire body before reaching the target tissue; instead, they could act in close proximity to the wound site. Such localized delivery may not only improve therapeutic efficacy but also reduce unwanted effects on healthy tissues elsewhere in the body.
Although considerable work remains before these materials can be translated into clinical practice, such studies already suggest a promising new direction for biomedical materials. Future therapeutic materials may no longer function merely as passive fillers, but instead behave more like living tissues themselves—soft, adaptive, flowable, and actively involved in the body’s own healing processes.

• author: Hou, Jingdan
• supervisor: Stefan Ulvenlund
• organization: Pharmaceutical Technology (master); Food Technology and Nutrition (M.Sc.)
• course: KLGM06 20261
• year: 2026
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: Supramolecular hydrogels, Cyclodextrin, Host–guest interactions, Nonionic surfactants, Injectable biomaterials, Rheological properties, Drug delivery, Curcumin release, Pharmaceutical formulation
• language: English
• id: 9237107
• date added to LUP: 2026-06-16 14:47:52
• date last changed: 2026-06-16 14:47:52