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Thursday, December 7, 2023

Frozen strengthened microneedles loaded with NIR-photothermal nanozyme for keratitis therapy


Bacterial keratitis, often known as bacterial corneal ulcers, is a type of corneal irritation attributable to bacterial infections, similar to Staphylococcus, Streptococcus, Streptococcus, and Pseudomonas [1], [2], [3]. The improper or ineffective therapy of bacterial keratitis might result in corneal perforations, intraocular infections, and finally irreversible visible impairment and blindness [4], [5]. Antibiotic eye drops are essentially the most broadly used remedy for treating bacterial keratitis. Nevertheless, because of the presence of the distinctive anatomical and physiological, structural traits of the cornea, such because the tight junction within the epithelium, the drug inside the eye drop shall be launched quickly after topical administration, with a brief resistance time and poor bioavailability [2], [6], [7]. As well as, the misuse of antibiotics has resulted within the emergence of antibiotic-resistant micro organism, overshadowing the way forward for antibiotic-based therapy. In distinction, intraocular injection based mostly on a standard hypodermic needle can penetrate the floor barrier and enhance topical supply with extended drug resistance, whereas affected person compliance is poor due to the ache, frequent visits requirement, and danger of an infection and bleeding [8], [9], [10]. Thus, ocular supply of localized, persistent, and extremely efficient antimicrobial brokers, in addition to favorable affected person compliance, is very anticipated for treating bacterial keratitis.

Herein, we current novel frozen strengthened microneedles (FR-MNs) loaded with near-infrared (NIR)-photothermal nanozyme for keratitis therapy, as schemed in Fig. 1. Nanozymes denote nanomaterials with mimetic enzyme exercise [11], [12], [13], [14], [15], [16]. Due to the convenience of preparation, regulated catalytic exercise, excessive stability, cost-effectiveness, and facile dealing with, nanozymes have change into promising alternate options to pure enzymes in numerous functions [17], [18], [19], [20], [21], [22]. Particularly, the nanozymes assembled by iron ion and polyhydric phenol have exhibited wonderful biocompatibility, biodegradability, pH-dependent catalytic exercise, and reactive oxygen species (ROS) formation or scavenging talents [23], [24]. Nevertheless, successfully and regionally delivering these nanozymes to the ocular floor stays a problem. Alternatively, microneedles (MNs) are an array of tiny needles with a micron scale, which have been broadly used to penetrate the epidermal for painless, non-invasive, and extremely environment friendly transdermal drug supply [25], [26], [27], [28], [29], [30], [31], [32]. Medication, practical cytokines, stem cells, proteins, two-dimensional supplies, and metal-organic framework supplies have been integrated inside MNs for numerous therapeutic functions [33], [34], [35], [36], [37]. Nonetheless, some MNs methods from pure polymers are too mushy to achieve sufficient tissue-piercing power. Thus, the best way to improve the mechanical power to make sure that the MNs can penetrate tissues and on the identical time obtain adaptive softening after penetration is a problem for MNs when utilized in mushy tissues.

On this paper, we loaded nanozymes into the tip of separable FR-MNs to achieve the ocular floor penetration necessities and to attain controllable formation and supply of ROS for bacterial keratitis therapy with the synergistic impact of photothermal remedy. Biocompatible methacrylate anhydride-modified recombinant human collagen (RHCMA) was chosen because the tip materials of such MNs. The nanozymes with a diameter of two nm have been constructed by the coordination reactions of iron ions, tannic acid (TA), and polyvinylpyrrolidone (PVP), which we termed FeTAP nanodots. The freezing course of may considerably improve the mechanical power of the MNs ideas. As a result of good thing about the pH-dependent peroxidase-mimetic actions of FeTAP, the built-in MNs may catalyze hydrogen peroxide (H2O2) to supply rather more oxidative hydroxyl (•OH) in acidic circumstances to kill micro organism. In the meantime, the wonderful photothermal effectivity of FeTAP can additional improve the flexibility of bacterial killing beneath near-infrared (NIR) irradiation. As well as, the photothermal motion may quickly enhance the temperature of the frozen microneedles and subsequently soften the MNs after penetration, which can lead to higher adaptation of MNs to mushy tissues. We’ve got verified that our proposed formulation confirmed superior therapeutic potential within the rat eye an infection mannequin in contrast with typical eye drops. These outcomes indicated that our nanozymes-loaded FR-MNs have scientific values for keratitis and will discover functions in quite a lot of related biomedical fields.

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