Injectable bio-responsive hydrogel for therapy of inflammation related eyelid diseases

Abstract

Eyelid plays a vital role in protecting the eye from injury or infection. Inflammation related eyelid diseases, such as blepharitis, are the most common ocular disorders that affect human's vision and quality of life. Due to the physiological barriers and anatomical structures of the eye, the bioavailability of topical administrated therapeutics is typically less than 5%. Herein, we developed a bio-responsive hydrogel drug delivery system using a generally recognized as safe compound, triglycerol monostearate (TG-18), for in-situ eyelid injection with sustained therapeutics release. In vitro, drug release and disassembly time of Rosiglitazone loaded hydrogel (Rosi-hydrogel) were estimated in the presence or absence of MMP-9, respectively. Moreover, the disassembly of TG-18 hydrogel was evaluated with 9-month-old and 12-month-old mice in vivo. Owing to the bio-responsive nature of Rosi-hydrogel, the on-demand Rosiglitazone release is achieved in response to local enzymes. These findings are proved by further evaluation in the age-related meibomian gland dysfunction mice model, and the bio-responsive hydrogel is used as an in-situ injection to treat eyelid diseases. Taken together, the in-situ eyelid injection with sustained drug release opens a window for the therapy of inflammation related eyelid diseases.

Local Elimination of Senescent Cells Promotes Bone Defect Repair during Aging

“…At last, we also examined the rheological properties of blank and quercetin hydrogels. The temperature sweep measurements demonstrated that the gelation temperature ( G ′ = G ″) was 56.05 °C for the blank hydrogel and 58.02 °C for quercetin hydrogel (SI Figure S8a), which suggested that the sol–gel transition of TG-18 occurred at approximately 60 °C . The frequency sweep measurements indicated that both blank and quercetin hydrogels were stable hydrogels since the G ′ value was always higher than their own G ″ value (SI Figure S8b).…”

“…The temperature sweep measurements demonstrated that the gelation temperature (G′ = G″) was 56.05 °C for the blank hydrogel and 58.02 °C for quercetin hydrogel (SI Figure S8a), which suggested that the sol−gel transition of TG-18 occurred at approximately 60 °C. 35 The frequency sweep measurements indicated that both blank and quercetin hydrogels were stable hydrogels since the G′ value was always higher than their own G″ value (SI Figure S8b). The time sweep measurements suggested that the structure of blank and quercetin hydrogel did not change under the constant shear forces as the G′ were higher than their own G″ (SI Figure S8c).…”

“…18,35,36 Notably, MMPs are essential initiators for the degeneration of TG-18 hydrogel. 18,35,36 Therefore, we designed an MMPs-responsive hydrogel by TG-18, which was expected to locally release quercetin in the microenvironment of senescent cells (Figure 5a). The hydrogel was prepared by the self-assembling of TG-18 molecular, 18 which could be cleaved by the MMPs at the ester bond (Figure 5c).…”

“…According to the recent literature, the TG-18 hydrogel has emerged as an excellent enzyme-responsive carrier to encapsulate drugs for local application, and applied to several diseases including arthritis, conjunctivitis, and brain trauma healing. ,, Notably, MMPs are essential initiators for the degeneration of TG-18 hydrogel. ,, Therefore, we designed an MMPs-responsive hydrogel by TG-18, which was expected to locally release quercetin in the microenvironment of senescent cells (Figure a). The hydrogel was prepared by the self-assembling of TG-18 molecular, which could be cleaved by the MMPs at the ester bond (Figure c).…”

An injectable and self-healing hydrogel with antibacterial and angiogenic properties for diabetic wound healing

“…The results showed a decrease in the viscosity as the frequency swept from 0.1 to 100 rad s −1 , which confirmed the shear thinning property of the hydrogels and that they could pass through microneedles easily. 40 The effect of metal ion cross-linking on the morphology of the hydrogels was directly demonstrated via scanning electron microscopy (SEM) (Fig. 1a).…”