Novel hyaluronic acid–methotrexate conjugates for osteoarthritis treatment

Homma, Akie; Sato, Haruhiko; Okamachi, Akira; Emura, Takashi; Ishizawa, Takenori; Kato, Tatsuya; Matsuura, Tetsu; Sato, Shigeo; Tamura, Tatsuya; Higuchi, Y.; Watanabe, Tomoyuki; Kitamura, Hidetomo; Asanuma, Kentaro; Yamazaki, Takeaki; Ikemi, Masahisa; Kitagawa, Haruaki; Morikawa, Takao; Ikeya, Hitoshi; Maeda, Kazuaki; Takahashi, Koichi; Nohmi, Kenji; Izutani, Noriyuki; Kanda, Makoto; Suzuki, Ryochi

doi:10.1016/j.bmc.2009.04.063

Cited by 72 publications

(45 citation statements)

References 54 publications

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“…21 An alternative intra-articular approach was tested in rats, in which MTX was complexed with hyaluronic acid; this was also not successful in treating the inflammation due to fast clearance from the joint cavity. 22 Liposome technology was also attempted to preserve MTX efficacy when injected intra-articularly. The uptake by rabbit synovial tissues of MTX enveloped in liposome systems was low, but yet greater than MTX alone.…”

Section: Discussionmentioning

confidence: 99%

Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

Mello¹,

Tavares²,

Bulgarelli³

et al. 2013

IJN

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Section: Discussionmentioning

confidence: 99%

Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

Mello¹,

Tavares²,

Bulgarelli³

et al. 2013

IJN

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“…In contrast, intra-articularly injected free MTX and the mixture of HA and MTX showed little or no effect. Of note, the conjugate with the Gly-Phe-Leu-Gly peptide linker (Figure 8), with a similar MTX loading, showed only a slight tendency to inhibit knee swelling, this suggesting that cleavage of the conjugate in vivo depends on the peptide sequence [18]. Figure 8.…”

Section: Ha Anti-inflammatory Drugmentioning

confidence: 98%

“…HA-MTX conjugate was also synthesized by Homma and co-workers (Chugai Pharmaceuticals Co., Tokio, Japan) for the delivery of MTX into the synovium, aiming to reach low systemic side effects after intra-articular administration [18]. In this attempt, MTX was firstly linked to a lysosomal enzyme-sensitive peptide linker.…”

Section: Ha Anti-inflammatory Drugmentioning

confidence: 99%

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Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

2014

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Hyaluronic acid (HA) has currently several therapeutic applications: in ophthalmology, osteoarthritis, wound healing, tissue regeneration, postoperative anti-adhesion and anesthetic medicine. In the last ten years, it has also been successfully investigated in the field of drug delivery, in the form of conjugates or hydrogel depot systems. HAylation, the covalent conjugation of HA to bioactive molecules, allows the overcoming of disadvantages associated with some pharmaceuticals, such as insolubility, instability and fast kidney clearance. These issues can be addressed also by covalent attachment of polyethylene glycol (PEGylation), but HA has the relevant advantages of biodegradability, high loading and specific targeting. In this review, the novel HA derivatives and the latest advances in HA-based drug delivery with a particular focus on the chemistry of conjugation will be discussed. Although, so far, there are no HA-drug conjugates on the market, several derivatives are presently under clinical investigation, and the promising results encourage further investigations and the exploitation of this versatile polysaccharide.

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“…Its clinical safety is well established, and it is also contained in several injectable products for cosmetic applications [70]. To date, HA's potential for use in drug delivery systems has been investigated as a carrier of anti-tumoral and anti-inflammatory drugs [71,72]. The conjugation of biologically active substances to HA is straightforward through a direct activation of the carboxylic acid groups present along the polymer backbone.…”

Section: Hyaluronic Acid (Ha)mentioning

confidence: 99%

Polymers for Protein Conjugation

Pasut

2014

Polymers

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Polyethylene glycol (PEG) at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

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Novel hyaluronic acid–methotrexate conjugates for osteoarthritis treatment

Cited by 72 publications

References 54 publications

Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

Polymers for Protein Conjugation

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