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.
Tarsal plate regeneration has always been a challenge in the treatment of eyelid defects. The commonly used clinical treatments such as hard palate mucosa grafts cannot achieve satisfactory repair effects. Tissue engineering has been considered as a promising technology. However, tarsal plate tissue engineering is difficult to achieve due to its complex structure and lipid secretion function. Three-dimensional (3D) printing technology has played a revolutionary role in tissue engineering because it can fabricate complex scaffolds through computer aided design (CAD). In this study, it was novel in applying 3D printing technology to the fabrication of tarsal plate scaffolds using poly-caprolactone (PCL). The decellularized matrix of adipose-derived mesenchymal stromal cells (DMA) was coated on the surface of the scaffold, and its biofunction was further studied. Immortalized human SZ95 sebocytes were seeded on the scaffolds so that neutral lipids were secreted for replacing meibocytes. In vitro experiments revealed excellent biocompatibility of DMA-PCL scaffolds with sebocytes. In vivo experiments revealed excellent sebocytes proliferation on the DMA-PCL scaffolds. Meanwhile, sebocytes seeded on the scaffolds secreted abundant neutral lipid in vitro and in vivo. In conclusion, a 3D-printed PCL scaffold modified with DMA was found to be a promising substitute for tarsal plate tissue engineering.
Ocular drug delivery has constantly challenged ophthalmologists and drug delivery scientists due to various anatomical and physiological barriers. Static and dynamic ocular barriers prevent the entry of exogenous substances and impede therapeutic agents' active absorption. This review elaborates on the anatomy of the eye and the associated constraints. Followed by an illustration of some common ocular diseases, including glaucoma and their current clinical therapies, emphasizing the significance of drug therapy in treating ocular diseases. Subsequently, advances in ocular drug delivery modalities, especially nanotechnology-based ocular drug delivery systems, are recommended, and some typical research is highlighted. Based on the related research, systematic and comprehensive characterizations of the nanocarriers are summarized, hoping to assist with future research. Besides, we summarize the nanotechnology-based ophthalmic drugs currently on the market or still in clinical trials and the recent patents of nanocarriers. Finally, inspired by current trends and therapeutic concepts, we provide an insight into the challenges faced by novel ocular drug delivery systems and further put forward directions for future research. We hope this review can provide inspiration and motivation for better design and development of novel ophthalmic formulations.
Graphical abstract
Decellularized matrix of ADMSCs is a promising conjunctival substitute with superb wound repairing property by promoting proliferation of conjunctival epithelial cells and restoring goblet cells without causing cosmetic differences.
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