Controlled release of dexamethasone sodium phosphate with biodegradable nanoparticles for preventing experimental corneal neovascularization

Wang, Bing; Tang, Ya-Ting; Oh, You-Take; Lamb, Nicholas W.; Xia, Shiyu; Ding, Zheng; Chen, Baiwei; Suárez, María; Meng, Tuo; Kulkarni, Vineet; Eberhart, Charles G.; Ensign, Laura M.; Stark, Walter J.; Xu, Qingguo

doi:10.1016/j.nano.2019.01.001

Cited by 38 publications

(32 citation statements)

References 24 publications

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“…Such long-acting formulations for DexSP administration can be prepared only when synthetic, non-swellable polymers are used. Such examples have been reported in literature using poly(ethylene glycol) (PEG) with zinc ion bridging [ 118 ] for DexSP nanoencapsulation and PLGA microspheres [ 119 , 120 ] where DexSP was released up to 25 and 30 days, respectively. Similar extended release profiles of Dex have been reported for intracanalicular applications (up to 30 days) [ 121 ] and up to 12 days from poly(ɛ-caprolactone) nanofibers [ 122 ].…”

Section: Resultsmentioning

confidence: 99%

Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs

et al. 2020

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The aim of this work was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with 2-acrylamido-2-methyl-1-propanesulfonic acid (AAMPS) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSP) as appropriate nanocarriers for the simultaneous ocular administration of dexamethasone sodium phosphate (DxP) and chloramphenicol (CHL). The derivatives CS-AAMPS and CS-MEDSP have been synthesized by free-radical polymerization and their structure has been proved by Fourier-Transformed Infrared Spectroscopy (FT-IR) spectroscopy. Both derivatives exhibited low cytotoxicity, enhanced mucoadhesive properties and antimicrobial activity against Staphylococcus aureus (S.aureus) and Escherichia coli (E. coli). Encapsulation was performed via ionic crosslinking gelation using sodium tripolyphosphate (TPP) as the crosslinking agent. Dynamic light scattering measurements (DLS) showed that the prepared nanoparticles had bimodal distribution and sizes ranging from 50–200 nm and 300–800 nm. Drugs were encapsulated in their crystalline (CHL) or amorphous (DexSP) form inside nanoparticles and their release rate was dependent on the used polymer. The CHL dissolution rate was substantially enhanced compared to the neat drug and the release time was extended up to 7 days. The release rate of DexSP was much faster than that of CHL and was prolonged up to 3 days. Drug release modeling unveiled that diffusion is the main release mechanism for both drugs. Both prepared derivatives and their drug-loaded nanoparticles could be used for extended and simultaneous ocular release formulations of DexSP and CHL drugs.

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Section: Resultsmentioning

confidence: 99%

Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs

et al. 2020

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“…We previously described approaches for loading water soluble dexamethasone sodium phosphate and sunitinib malate into polymeric particles for subconjunctival injection, providing sustained prevention or treatment of corneal graft rejection [ 42 ], corneal neovascularization [ 25 , 45 ] and uveitis [ 24 ]. However, one potential drawback was relatively low drug loading in the range of 6–8% by weight.…”

Section: Discussionmentioning

confidence: 99%

Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

et al. 2021

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Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

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“…Various nanocarriers/microcarriers with sustained drug delivery capability have been developed in recent years for ocular use [ 20 , 21 ]. Due to their size, and flexible surface functionality, nanocarriers/microcarriers offer advantages in drug delivery for the treatment of posterior eye diseases [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Controlled release of dexamethasone sodium phosphate with biodegradable nanoparticles for preventing experimental corneal neovascularization

Cited by 38 publications

References 24 publications

Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs

Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs

Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

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

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