A Long-Acting Curcumin Nanoparticle/In Situ Hydrogel Composite for the Treatment of Uveal Melanoma

Uveal melanoma (UM) is the most common primary intraocular tumor in adults with high mortality. In order to improve prognosis and survival of UM patients, it is critical to inhibit tumor progression and metastasis as early as possible after the initial presentation/diagnosis of the disease. Sustained local delivery of antitumor therapeutics in the posterior region can potentially achieve long-term UM inhibition, improve target therapeutic delivery to the posterior segments, as well as reduce injection frequency and hence improved patient compliance. To address the highly unmet medical need in UM therapy, a bioinspired in situ gelling hydrogel system composed of naturally occurring biopolymers collagen and hyaluronic acid was developed in the present research. Curcumin with anti-cancer progression, anti-metastasis effects, and good ocular safety was chosen as the model therapeutic. The developed in situ gelling delivery system gelled at 37 °C within two minutes and demonstrated excellent biocompatibility and slow degradation. The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer.

Efficacy and Safety of Azelaic Acid Nanocrystal-Loaded In Situ Hydrogel in the Treatment of Acne Vulgaris

Acne vulgaris is a common, multifactorial, inflammatory skin disease affecting the pilosebaceous unit. Topical therapy is the first choice in the treatment of mild to moderate acne, and azelaic acid (AZA) is one of the most commonly used drugs. The aim of this study was to evaluate the safety and efficacy of a low-dose azelaic acid nanocrystal (AZA-NC) hydrogel in the treatment of mild to moderate facial acne. The study was designed as a double-blind, randomized controlled trial. Patients were randomized to treatment with AZA-NC hydrogel, 10%, or AZA cream, 20%, administered in quantities of approximately 1 g twice daily for 8 weeks. Efficacy of therapy was measured by the number of lesions and safety by the frequency and severity of adverse events. At week 8, the success rate of treatment with AZA-NC hydrogel, 10%, was 36.51% (p < 0.001) versus 30.37% (p < 0.001) with AZA cream. At week 8, treatment with AZA-NC hydrogel, 10%, resulted in a significant reduction in total inflammatory lesions from baseline of 39.15% (p < 0.001) versus 33.76% (p < 0.001) with AZA cream, and a reduction in non-inflammatory lesions from baseline of 34.58% (p < 0.001) versus 27.96% (p < 0.001) with AZA cream, respectively. The adverse event rate was low and mostly mild.

Effects of Gamma Radiation on the Sterility Assurance, Antibacterial Ability, and Biocompatibility of Impregnated Hydrogel Macrosphere Protein and Drug Release

Devices and medicines used in the medical field must be sterile. Gamma (γ)-irradiation is commonly used for sterilization because its high rate of penetration ensures uniform sterilization. To confirm that hydrogel macrosphere carriers inherit excellent liquid absorption with no cytotoxicity after γ-irradiation sterilization, investigating whether the physiochemical properties of hydrogel macrospheres differ before and after sterilization is essential. The present study evaluated the influence of the recommended 25-kGy γ-irradiation dose on the physicochemical characteristics and in vitro release of bovine serum albumin and vancomycin (an antibiotic medication) from alginate/gelatin with a w/w ratio of 1/4 crosslinking gel macrospheres. Gel macrosphere properties before and after sterilization were compared according to optical and scanning electron microscopy, infrared spectroscopy analysis, the amino residual crosslinking index, water absorption, degradation, sterility assurance, in vitro drug release, antibacterial ability, and cytotoxicity. The crosslinking index was almost unchanged; however, the γ-irradiation caused in situ hydrogel debonding and recrosslinking, which led to a decrease in the water absorption and increase in the degradation rate of the macrospheres after immersion. The release of gel macrospheres carrying vancomycin did not significantly affect antibacterial ability or biocompatibility after γ-irradiation. Accordingly, we conclude that γ-irradiation is suitable for macrospherical formulation.