Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis

Alam, Mohammad Zahangir; Han, Hwa Seung; Sung, Su Whan; Kang, Jung Hoon; Hee, Keum; Faruque, Hasan Al; Hong, Ji Won; Nam, Eon Jeong; Kim, In San; Park, Jae Hyung; Kang, Young Mo

doi:10.1016/j.jconrel.2017.03.012

Cited by 86 publications

(41 citation statements)

References 45 publications

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“…The concept guiding the development of TG-18 hydrogel has been to generate an intra-articular drug reservoir which releases drug in response to enzymes overexpressed in inflamed joints. Prior studies of inflammation-responsive drug delivery systems in IA relied on polymeric particles releasing drug cargo in response to the low pH in inflamed synovial fluid 25 – 27 . These drug-loaded particles were administered systemically and entered inflamed joints from the blood stream.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, intravenously injected nano- and microparticles tend to accumulate in the liver and spleen via the reticuloendothelial system 26 , increasing the risk for toxic side effects. Finally, the synthesis of pH-responsive polymer conjugates like hyaluronic acid-5 β -cholanic acid conjugate based nanoparticles 27 and N -(2-hydroxypropyl)methacrylamide copolymer-dexamethasone conjugate 28 , 29 is complex, which limits scalability and translatability. TG-18 on the other hand, can be coaxed to form self-assembling hydrogel using a simple process.…”

Section: Discussionmentioning

confidence: 99%

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Towards an arthritis flare-responsive drug delivery system

et al. 2018

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Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent dye demonstrates flare-dependent disassembly measured as loss of fluorescence. Moreover, a single dose of TA-loaded hydrogel but not the equivalent dose of locally injected free TA reduces arthritis activity in the injected paw. Together, our data suggest flare-responsive hydrogel as a promising next-generation drug delivery approach for the treatment of IA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Towards an arthritis flare-responsive drug delivery system

et al. 2018

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“…Taken together, HA‐based NPs can be utilized for diseases including various kinds of cancer, RA, and diabetes, as carriers for chemotherapy (CHT), photodynamic therapy, and photothermal therapy, along with carriers for biologics such as siRNA and applications in immunotherapy (IMT) ( Table 3 ). In the end, these examples demonstrate the diverse possibilities available by using HA‐based NPs as actively targeted carriers and/or triggered delivery systems in response to Hyal overexpression at localized sites of disease.…”

Section: Stimuli‐responsive Nanomaterials Based On Hyaluronic Acidmentioning

confidence: 99%

Hyaluronic Acid–Based Activatable Nanomaterials for Stimuli‐Responsive Imaging and Therapeutics: Beyond CD44‐Mediated Drug Delivery

et al. 2019

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There is a rapidly increasing interest in developing stimuli-responsive nanomaterials for treating a variety of diseases. By enabling the activation of function locally at the sites of interest, it is possible to increase therapeutic efficacy significantly while simultaneously reducing adverse side effects. While there are many sophisticated nanomaterials available, they are often highly complex and not easily transferrable to industrial scales and clinical settings. However, nanomaterials based on hyaluronic acid offer a compelling strategy for reducing their complexity while retaining several desirable benefits such as active targeting and stimuli-responsive degradation. Herein, the basic properties of hyaluronic acid, its binding partners, and natural routes for degradation by hyaluronidases-hyaluronic-aciddegrading enzymes-and oxidative stresses are discussed. Recent advances in designing hyaluronic acid-based, actively targeted, hyaluronidase-or reactive-oxygen-species-responsive nanomaterials for both diagnostic imaging and therapeutic delivery, which go beyond merely the classical targeting of CD44, are summarized.

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“…HACA was prepared using EDC/NHS chemistry. For this chemistry, the amine derivative of CA was prepared as previously reported [31][32][33]. Then, the aminated CA was chemically conjugated to the HA backbone.…”

Section: Synthesis Of Amphiphilic Ha Derivative (Haca)mentioning

confidence: 99%

Metal-Phenolic Network-Coated Hyaluronic Acid Nanoparticles for pH-Responsive Drug Delivery

et al. 2019

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Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which consist of an amphiphilic hyaluronic acid derivative, were prepared to be a pH-responsive nanocarrier to facilitate drug release in tumor microenvironments (TME). Due to their amphiphilic nature, SNPs were capable of encapsulating doxorubicin (DOX), chosen as the model anticancer drug. Tannic acid and FeCl3 were added to the surface of the DOX-SNPs, which allowed them to be readily coated with MPNs as the diffusion barrier. The pH-sensitive MPN corona allowed for a rapid release of DOX and effective cellular SNP uptake in the mildly acidic condition (pH 6.5) mimicking TME, to which the hyaluronic acid was exposed to facilitate receptor-mediated endocytosis. The DOX-loaded MPN-SNPs exhibited a higher cytotoxicity for the cancer cells, suggesting their potential use as a drug carrier in targeted cancer therapy.

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Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis

Cited by 86 publications

References 45 publications

Towards an arthritis flare-responsive drug delivery system

Towards an arthritis flare-responsive drug delivery system

Hyaluronic Acid–Based Activatable Nanomaterials for Stimuli‐Responsive Imaging and Therapeutics: Beyond CD44‐Mediated Drug Delivery

Metal-Phenolic Network-Coated Hyaluronic Acid Nanoparticles for pH-Responsive Drug Delivery

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