Lyotropic liquid crystals (LLCs) formed by the self-assembly of amphiphilic molecules in a solvent (usually water) have attracted increasingly greater attention in the last few decades, especially the lamellar phase (L_α), the reversed bicontinuous cubic phase (Q₂) and the reversed hexagonal phase (H₂). Such phases offer promising prospects for encapsulation of a wide range of target molecules with various sizes and polarities owing to the unique internal structures. Also, different structures of mesophases can give rise to different diffusion coefficients. The bicontinuous cubic phase and the hexagonal phase have been demonstrated to control and sustain the release of active molecules. Furthermore, the structures are susceptible to many factors such as water content, temperature, pH, the presence of additives etc. Many researchers have been studying these influencing factors in order to accurately fabricate the desired phase. In this paper, we give a review of the characteristics of different structures of liquid crystalline phases, the influencing factors on the phase transition of liquid crystals and the relationship between structures of LLC and drug diffusion. We hope our review will provide some insights into how to manipulate in a controlled manner the rate of incorporating and transferring molecules by altering the structure of lyotropic mesophases.

Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed.

Periodontitis is a chronic inflammatory disease initiated by pathogenic biofilms and host immunity that damages tooth-supporting tissues, including the gingiva, periodontal ligament and alveolar bone. The physiological functions of the oral cavity, such as saliva secretion and chewing, greatly reduce the residence of therapeutic drugs in the area of a periodontal lesion. In addition, complex and diverse pathogenic mechanisms make effectively treating periodontitis difficult. Therefore, designing advanced local drug delivery systems and rational therapeutic strategies are the basis for successful periodontitis treatment. Hydrogels have attracted considerable interest in the field of periodontitis treatment due to their biocompatibility, biodegradability and convenient administration to the periodontal pocket. In recent years, the focus of hydrogel research has shifted to smart stimuli-responsive hydrogels, which can undergo flexible sol-gel transitions in situ and control drug release in response to stimulation by temperature, light, pH, ROS, glucose, or enzymes. In this review, we systematically introduce the development and rational design of emerging smart stimuli-responsive hydrogels for periodontitis treatment. We also discuss the state-of-the-art therapeutic strategies of smart hydrogels based on the pathogenesis of periodontitis. Additionally, the challenges and future research directions of smart hydrogels for periodontitis treatment are discussed from the perspective of developing efficient hydrogel delivery systems and potential clinical applications.

Periodontitis is a chronic inflammatory disease caused by the local microbiome and the host immune response, resulting in periodontal structure damage and even tooth loss. Scaling and root planning combined with antibiotics are the conventional means of nonsurgical treatment of periodontitis, but they are insufficient to fully heal periodontitis due to intractable bacterial attachment and drug resistance. Novel and effective therapeutic options in clinical drug therapy remain scarce. Nanotherapeutics achieve stable cell targeting, oral retention and smart release by great flexibility in changing the chemical composition or physical characteristics of nanoparticles. Meanwhile, the protectiveness and high surface area to volume ratio of nanoparticles enable high drug loading, ensuring a remarkable therapeutic efficacy. Currently, the combination of advanced nanoparticles and novel therapeutic strategies is the most active research area in periodontitis treatment. In this review, we first introduce the pathogenesis of periodontitis, and then summarize the state-of-the-art nanotherapeutic strategies based on the triple concerto of antibacterial activity, immunomodulation and periodontium regeneration, particularly focusing on the therapeutic mechanism and ingenious design of nanomedicines. Finally, the challenges and prospects of nano therapy for periodontitis are discussed from the perspective of current treatment problems and future development trends. Graphical Abstract