Evaluation of His₆-Metal Assemblies as a Drug Delivery Vehicle in the Treatment of Anterior Segment Disease Using a Corneal Inflammation Model

Abstract

Keratitis is a common ophthalmological disease and also a common cause of blindness (second only to cataracts). This disease is routinely treated by topical administration of dexamethasone sodium phosphate (Dexp). However, due to the presence of anatomical and physiological barriers, frequent administration is needed, often resulting in poor patient compliance and diverse side effects. In this work, Dexp was in situ encapsulated into a His 6 -metal assembly (HmA) to generate Dexp@ HmA, which was utilized in the ocular delivery of Dexp. The physicochemical properties of HmA and Dexp@HmA particles were characterized in detail using various techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV−vis spectroscopy. Compared to commercial Eudragi and reported PLGA nanoparticles, HmA showed higher encapsulation efficiency (EE%) and higher loading capacity (LC wt %) of Dexp. Dexp@HmA displayed pH-dependent release; after 33 days at pH 5.8, 6.5, and 7.2, 100%, 65%, and 42% of Dexp, respectively, had been released. In addition, HmA and Dexp@HmA showed low cytotoxicity to macrophages and to all common ocular cell types tested. The effect of Dexp@HmA on corneal inflammation was evaluated using in vitro and in vivo models. Our results demonstrate that Dexp@HmA is much superior to free Dexp in both in vitro and in vivo models. These positive results suggest that HmA may represent a promising candidate nanocarrier for the treatment of various diseases of the anterior segment of the eye.

Combined delivery of small molecule and protein drugs as synergistic therapeutics for treating corneal neovascularization by a one-pot coassembly strategy

“…As shown in Fig. 2 a, the absorbances at 240 ​nm and 280 ​nm were attributed to Dexp and BVZ [ 25 , 26 ], respectively, which were observed in Dexp&BVZ@HmA. The encapsulation of Dexp and BVZ into HmA was also supported by the FTIR spectra.…”

“…To address the above issues, we utilized the hexahistidine-metal assembly (HmA) formed through coordinative interaction between side imidazole group of hexahistidine and metal ions at mild conditions, which displayed encapsulating a wide spectrum of drugs with high loading efficiency [ 24 ], to coencapsulate Dexp and BVZ by a one-pot coassembly strategy. In previous studies [ 25 , 26 ], HmA exhibited a promising candidate nanocarrier of Dexp and BVZ for treating disease in anterior segment. Here, our data demonstrated that Dexp and BVZ were coloaded into Dexp&BVZ@HmA with high efficiency, while the bioactivity of BVZ was well-maintained.…”

Deliver protein across bio-barriers via hexa-histidine metal assemblies for therapy: a case in corneal neovascularization model

“…In addition, the alkali burn model has low cost and easy operation [ 37 ]. Alkali burn–induced CNV is the most widely used model in the study of CNV [ [38] , [39] , [40] ].…”

One-Pot Generating Subunit Vaccine with High Encapsulating Efficiency and Fast Lysosome Escape for Potent Cellular Immune Response

“…Metal–Organic frames (MOFs) formed by coordinative interaction between metal ions and organic ligands have attracted more and more attention as drug delivery vehicles because of their facile and mild generation conditions, tunable structure, abundant assembly materials, efficient encapsulation of various materials, etc. , Encapsulating adjuvant (CpG) into the zeolitic imidazolate framework-8 (ZIF-8) had been demonstrated as subunit vaccines with potent humoral and cellular immune responses . In previous work, we reported a promising delivery system based on hexa-histidine (His 6 ) metal assemblies (HmA), which can encapsulate various drugs at mild conditions, featuring fast endocytosis and lysozyme escape. , Here, utilizing HmA, for the first time, we presented a one-pot synthesis of a subunit vaccine with a high coencapsulation efficiency and fast lysosome escape of antigen (GP100, a peptide KTWGQ­YWQV) and adjuvant (CpG ODN 1826). Our results demonstrated such generated subunit vaccines could enhance the maturation of antigen-presenting cells and stimulation of potent cellular immune response, and the strategy developed here could contribute to the future design in a subunit vaccine.…”

“…27 In previous work, we reported a promising delivery system based on hexa-histidine (His 6 ) metal assemblies (HmA), 28 which can encapsulate various drugs at mild conditions, featuring fast endocytosis and lysozyme escape. 29,30 Here, utilizing HmA, for the first time, we presented a one-pot synthesis of a subunit vaccine with a high coencapsulation efficiency and fast lysosome escape of antigen (GP100, a peptide KTWGQYWQV) and adjuvant (CpG ODN 1826). Our results demonstrated such generated subunit vaccines could enhance the maturation of antigen-presenting cells and stimulation of potent cellular immune response, and the strategy developed here could contribute to the future design in a subunit vaccine.…”