Dexamethasone sodium phosphate loaded nanoparticles for prevention of nitrogen mustard induced corneal injury.

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need. Herein, we aim to explore the sustained effect of Dexamethasone sodium phosphate (DSP)-loaded polymeric nanoparticles (PLGA-DSP-NP) following a single subconjunctival injection in the management and prevention of corneal injury progression upon exposure to NM. DSP is an FDA approved corticosteroid with proven anti-inflammatory properties. We formulated PLGA-DSP-NP with zinc chelation ion bridging method using PLGA polymer, with particles of approximately 250 nm and a drug loading of 6.5 wt%. Under in vitro sink conditions, PLGA-DSP-NP exhibited a sustained drug release for two weeks. Notably, in NM injured cornea, a single subconjunctival (SCT) injection of PLGA-DSP-NP outperformed DSP eyedrops (0.1%), DSP solution, placebo NP, and saline, significantly mitigating corneal neovascularization, ulceration, and opacity for the two weeks study period. Through PLGA-DSP-NP injection, sustained DSP release hindered inflammatory cytokine recruitment, angiogenic factors, and endothelial cell proliferation in the cornea. This strategy presents a promising localized corticosteroid delivery system to effectively combat NM-induced corneal injury, offering insights into managing vesicant exposure.

Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye.

Low bioavailability of topically applied drugs remains a significant challenge for long-term glaucoma therapy. To enhance drug delivery efficiency, we developed dendrimer gel particles that collectively exhibit structural benefits of dendrimer, hydrogel, and particles, using the inverse emulsion method coupled with the highly efficient aza-Michael addition reaction (IEaMA). This hierarchical approach would maximize the utility of the structural features of existing ocular drug delivery systems. We have tested the delivery efficiency and efficacy of two first-line antiglaucoma drugs, brimonidine tartrate (BT) and timolol maleate (TM), which were loaded into dendrimer gel particles of various sizes, i.e., nDHP (nano-in-nano dendrimer hydrogel particles, ~200 nm), µDHP3 (3 µm), and µDHP10 (9 µm). We found that nDHP was superior to µDHP3 and µDHP10 in terms of cytocompatibility, degradability, drug release kinetics, and corneal permeability. The nDHPs increased drug corneal permeability by 17-fold compared to plain drug solution and enabled zero-order prolonged drug release kinetics. The nDHP-based formulation demonstrated pronounced IOP-lowering effects in both single-dose test and 7-day chronic daily dosing test in both Brown Norway rats and glaucoma mice. Taken together, we have developed nano-in-nano dendrimer gel particles for precise dosing and enabling sustained and synergistic efficacy of antiglaucoma drugs, which could be clinically impactful for improving glaucoma treatment.

Dystrophic muscle distribution in late-stage muscular dystrophy.

There is scant information about the comprehensive distribution of dystrophic muscles in muscular dystrophy. Despite different clinical presentations of muscular dystrophy, a recent multi-center study concluded that phenotypic distribution of dystrophic muscles is independent of clinical phenotype and suggested that there is a common pattern of involved muscles. To evaluate this possibility, the present case report used cadaveric dissection to determine the whole-body distribution of fat-infiltrated, dystrophic muscles from a 72-year-old white male cadaver with adult-onset, late-stage muscular dystrophy. Severely dystrophic muscles occupied the pectoral, gluteal and pelvic regions, as well as the arm, thigh and posterior leg. In contrast, muscles of the head, neck, hands and feet largely appeared unaffected. Histopathology and a CT-scan supported these observations. This pattern of dystrophic muscles generally conformed with that described in the multi-center study, and provides prognostic insight for patients and the physicians treating them.

Dystrophic muscle distribution in late-stage muscular dystrophy

There is scant information about the comprehensive distribution of dystrophic muscles in muscular dystrophy. Despite different clinical presentations of muscular dystrophy, a recent multi-center study concluded that phenotypic distribution of dystrophic muscles is independent of clinical phenotype and suggested that there is a common pattern of involved muscles. To evaluate this possibility, the present case report used cadaveric dissection to determine the whole-body distribution of fat-infiltrated, dystrophic muscles from a 72-year-old white male cadaver with adult-onset, late-stage muscular dystrophy. Severely dystrophic muscles occupied the pectoral, gluteal and pelvic regions, as well as the arm, thigh and posterior leg. In contrast, muscles of the head, neck, hands and feet largely appeared unaffected. Histopathology and a CT-scan supported these observations. This pattern of dystrophic muscles generally conformed with that described in the multi-center study, and provides prognostic insight for patients and the physicians treating them.