Synthesis and Evaluation of Novel Polyester-Ibuprofen Conjugates for Modified Drug Release

Thompson, Colin J.; Hansford, Denise; Munday, D.L.; Higgins, S. J.; Rostron, C.; Hutcheon, Gillian A.

doi:10.1080/03639040801929075

Cited by 20 publications

(18 citation statements)

References 18 publications

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“…The lack of monomer present in the reaction mixture was confirmed by NMR and IR spectroscopies. Chloroform was chosen because it is the preferred solvent to terminate the lipase reactions; despite the use of this solvent in this one step, our overall synthetic methods are greener than traditional methods; other methods to achieve similar reactions utilize excess carbodiimides, chlorinated solvents, and metal catalysts often used in contrast to solvent‐free, catalytic reactions, safer solvents, and enzyme catalyst. GPC analysis indicated that M w values were moderate and PDI values narrow (Table ) substantiating that an additional purification step was unnecessary.…”

Section: Resultsmentioning

confidence: 99%

“…In systems where the drug is chemically incorporated into the polymer, non‐biodegradable polymers are often used, leading to potential adverse effects when used in vivo as the polymer may remain . In previous work, an ibuprofen‐containing polyester was prepared using N435 but had low drug loading (3–13%) and a burst release; 35% of ibuprofen was released after 18 d, but not thereafter . Polymers of sebacic acid, glycerol, poly(ethylene glycol), and ketoprofen have similarly been developed using N435; however, low drug loading (<25%) and the use of toxic, expensive vinyl moieties remain issues.…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic Polymerization of an Ibuprofen-Containing Monomer and Subsequent Drug Release

Stebbins

Uhrich

2015

Macromol. Biosci.

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Novel ibuprofen-containing monomers comprised of naturally occurring and biocompatible compounds were synthesized and subsequently polymerized via enzymatic methods. Through the use of a malic acid sugar backbone, ibuprofen was attached as a pendant group, and then subsequently polymerized with a linear aliphatic diol (1,3-propanediol, 1,5-pentanediol or 1,8-octanediol) as comonomer using lipase B from Candida antarctica, a greener alternative to traditional metal catalysts. Polymer structures were elucidated by nuclear magnetic resonance and infrared spectroscopies, and thermal properties and molecular weights were determined. All polymers exhibited sustained ibuprofen release, with the longer chain, more hydrophobic diols exhibiting the slowest release over the 30 day study. Polymers were deemed cytocompatible using mouse fibroblasts, when evaluated at relevant therapeutic concentrations. Additionally, ibuprofen retained its chemical integrity throughout the polymerization and in vitro hydrolytic degradation processes. This methodology of enzymatic polymerization of a drug presents a more environmentally friendly synthesis and a novel approach to bioactive polymer conjugates.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enzymatic Polymerization of an Ibuprofen-Containing Monomer and Subsequent Drug Release

Stebbins

Uhrich

2015

Macromol. Biosci.

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“…A novel therapeutic approach of OA consists of using intra-articular drug delivery systems (DDSs) with the ability to locally release NSAIDs 17 . Various formulations of DDS are currently investigated to achieve a sustained release of NSAIDs [18][19][20] . Intra-articular DDS should provide long-term sustained release of NSAIDs and diminish the amount of systemic drug exposition, which in turn reduces the relatedadverse events.…”

Section: Introductionmentioning

confidence: 99%

In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

Bédouet¹,

Pascale²,

Bonneau³

et al. 2013

Drug Development and Industrial Pharmacy

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Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the efficacy of S-(+)-ibuprofen on cartilage degradation as drug candidate for DDS loading. Humeral cartilage and joint capsule explants were collected from healthy sheep shoulder joints and they were cultured in mono- or in co-culture for 13 days with LPS in combination with S-(+)-ibuprofen at 50 µM and 1 mM. S-(+)-ibuprofen (50 µM) blocked prostaglandins production in LPS-activated explants but did not reduce cartilage degradation. By contrast, 1 mM S-(+)-ibuprofen treatment of cartilage explants reduced nitric oxide synthesis by 51% (p = 0.0072), proteoglycans degradation by 35% (p = 0.0114) and expression of serum amyloid protein - the main protein induced upon LPS challenge - by 44% (p < 0.0001). On contrary, in presence of synovial membrane, the protective effects of S-(+)-ibuprofen on cartilage damages were significantly diminished. At 1mM, S-(+)-ibuprofen reduced the cell lysis during culture of cartilage and joint capsule either in mono- or in co-culture. This study performed on sheep explants shows that 1 mM S-(+)-ibuprofen inhibited cartilage degradation via a mechanism independent of cyclooxygenase inhibition. Reduction of prostaglandins synthesis at 50 µM in all treatment groups and reduction of cartilage degradation observed at 1 mM suggest that S-(+)-ibuprofen could be considered as a promising drug candidate for the loading of intra-articular DDS.

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“…Previously, this has been demonstrated through functionalisation of PGA with N-acyl amino acids via Steglich Esterification [8]. Additionally, the drug molecules indomethacin [11], methotrexate [12] and ibuprofen [13] have been successfully coupled to the polymer backbone. The low toxicity of PGA coupled with the ease with which it can be synthesised, functionalised with drug molecules and formulated into nanoparticles means it shows great potential as a polymeric platform for both targeted and systemic drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Exploring the enzymatic degradation of poly(glycerol adipate)

Swainson

Taresco

Pearce

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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A B S T R A C TPoly(glycerol adipate) (PGA) is a biodegradable, biocompatible, polymer with a great deal of potential in the field of drug delivery. Active drug molecules can be conjugated to the polymer backbone or encapsulated in selfassembled nanoparticles for targeted and systemic delivery. Here, a range of techniques have been used to characterise the enzymatic degradation of PGA extensively for the first time and to provide an indication of the way the polymer will behave and release drug payloads in vivo. Dynamic Light Scattering was used to monitor change in nanoparticle size, indicative of degradation. The release of a fluorescent dye, coupled to PGA, upon incubation with enzymes was measured over a 96 h period as a model of drug release from polymer drug conjugates. The changes to the chemical structure and molecular weight of PGA following enzyme exposure were characterised using FTIR, NMR and GPC. These techniques provided evidence of the biodegradability of PGA, its susceptibility to degradation by a range of enzymes commonly found in the human body and the polymer's potential as a drug delivery platform.

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Synthesis and Evaluation of Novel Polyester-Ibuprofen Conjugates for Modified Drug Release

Cited by 20 publications

References 18 publications

Enzymatic Polymerization of an Ibuprofen-Containing Monomer and Subsequent Drug Release

Enzymatic Polymerization of an Ibuprofen-Containing Monomer and Subsequent Drug Release

In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

Exploring the enzymatic degradation of poly(glycerol adipate)

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