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

Abstract

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.

RETRACTED: A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy

“…When n was five, the compound was named TA6, n was seven, the compound was TA8, and n was eight, the compound was TA9. The 1 H-NMR and 13 C-NMR spectra of TA6, TA8, and TA9 were measured using a NMR spectrometer (Bruker AV-400, Karlsruhe Germany) with D 2 O and CD 3 OD as solvents. In addition, a mass spectrometer (MS, Thermo Fisher Scientific, Bremen, Germany) was used to obtain the mass spectra to characterize the structure of products.…”

“…The yield of TA6 was 96.83% and the melting point was 125-126 1H), 1.54 (dd, J = 14.1, 6.9 Hz, 2H), 1.36 (tt, J = 13.0, 6.5 Hz, 2H), 1.29-1.10 (m, 10H), 0.99 (dt, J = 12.8, 9.8 Hz, 2H), 0.80 (t, J = 6.9 Hz, 3H). 13 TA9 was synthesized as a white crystal. The yield of TA6 was 97.09% and the melting point was 130-131 • C. 1 H-NMR (600 MHz, D 2 O) δ 3.97 (t, J = 7.0 Hz, 2H), 2.84 (d, J = 7.0 Hz, 2H), 2.21 (dd, J = 19.9, 7.7 Hz, 1H), 1.90 (t, J = 13.9 Hz, 4H), 1.75-1.61 (m, 1H), 1.55 (dd, J = 13.4, 6.6 Hz, 2H), 1.47-1.32 (m, 2H), 1.14-1.31 (m, J = 18.1 Hz, 12H), 1.08-0.93 (m, 2H), 0.81 (t, J = 6.8 Hz, 3H).…”

“…The yield of TA6 was 97.09% and the melting point was 130-131 • C. 1 H-NMR (600 MHz, D 2 O) δ 3.97 (t, J = 7.0 Hz, 2H), 2.84 (d, J = 7.0 Hz, 2H), 2.21 (dd, J = 19.9, 7.7 Hz, 1H), 1.90 (t, J = 13.9 Hz, 4H), 1.75-1.61 (m, 1H), 1.55 (dd, J = 13.4, 6.6 Hz, 2H), 1.47-1.32 (m, 2H), 1.14-1.31 (m, J = 18.1 Hz, 12H), 1.08-0.93 (m, 2H), 0.81 (t, J = 6.8 Hz, 3H). 13…”

“…Injectable in situ gels are available to be applied directly at the lesion site to control drugs released locally and avoid many adverse reactions [11,12]. Traditional polymer gels with covalent bonds are commonly used but difficult to degrade in vivo [13]. LMWGs, which refer to the formation of low-molecular gelators through non-covalent bonds, have greater advantages [14].…”

Considerations for Polymers Used in Ocular Drug Delivery

“…Xie et al (173) developed a nanoparticle/hydrogel composite for the sustained release of an anti-tumor therapeutic to the posterior segment of the eye. The hydrogel, composed of collagen II and sodium hyaluronate, was formed in situ following injection in to the vitreous and in response to physiological temperature stimuli.…”