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Shaaya, Osnat; Magora, Amir; Sheskin, Tzviel; Kumar, Neeraj; Domb, Abraham J.

doi:10.1023/a:1022214919481

Cited by 17 publications

(6 citation statements)

References 9 publications

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“…(c) Preparation of mixed anhydrides of carboxylic acid-bearing drugs [9] to produce lipophilic and non-irritating prodrug forms, provided that the parent bioactive agent can be released from the prodrug at its sites of activity. (d) Formulation in microspheres containing cellulose acetate and polyethylene glycol [10] to control the release of Ibu, or (e) complexation with CyD [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Omari

Daraghmeh

El‐Barghouthi

et al. 2009

Journal of Pharmaceutical and Biomedical Analysis

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Section: Introductionmentioning

confidence: 99%

Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Omari

Daraghmeh

El‐Barghouthi

et al. 2009

Journal of Pharmaceutical and Biomedical Analysis

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“…A number of prodrugs of ibuprofen have been reported [14,15,16] but very few mutual prodrugs of dexibuprofen were reported [17,18]. The current study was undertaken to synthesize novel mutual prodrugs of dexibuprofen to reduce its gastrointestinal effects while maintaining the pharmacological profile.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Ashraf

Alamgeer

Rasool

et al. 2016

IJMS

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Dexibuprofen–antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a–c were obtained by reacting its –COOH group with chloroacetyl derivatives 3a–c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a–c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p < 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p < 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a–c interacts with the residues present in active binding sites of target protein. The stability of drug–target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug.

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“…Moreover, hydrolyzable IBU derivatives, such as amides [45] or anhydrides [46], were also synthesized in order to improve biopharmaceutical properties of the drug.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Properties of a Star-Shaped Poly( ϵ -Caprolactone)–Ibuprofen Conjugate

Olędzka

Kaliszewska

Sobczak

et al. 2012

Journal of Biomaterials Science, Polymer Edition

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A series of novel star-shaped poly(ϵ-caprolactone) (PCL) biodegradable polyesters were synthesized through ring-opening polymerization of ϵ-caprolactone in the presence of a poly(amidoamine) (PAMAM) dendrimer initiator. The polymers (PAMAM/PCLs) were obtained with a high yield (92%) and a number-average molecular weight of up to 14 000 g/mol. The nonlinear structure of PAMAM/PCLs was confirmed by nuclear magnetic resonance, gel-permeation chromatography, thermogravimetric analysis and differential scanning calorimetry. Thermal analysis indicated that the star-shaped PAMAM/PCLs had a melting point, degree of crystallinity, glass transition temperature and maximum decomposition temperature all lower than those of linear PCL. Ibuprofen (IBU), a popular non-steroidal anti-inflammatory drug, was co-valently (ester) bonded to the PAMAM/PCL molecules using the DCC/DMAP coupling method (DCC, N,N'-dicyclohexylcarbodiimide; DMAP, 4-(dimethylamino)pyridine). A high drug content (33.1 mol%) in the conjugate was obtained. The in-vitro drug-release profiles of IBU from the PAMAM/PCL/IBU conjugate were examined and found adequate for drug-carrier applications of our star-shaped polymers.

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Abstract: This study demonstrates the promise of anhydride prodrugs for extending drug action and shielding the carboxylic acid group.

Cited by 17 publications

References 9 publications

Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs

Synthesis and Properties of a Star-Shaped Poly( ϵ -Caprolactone)–Ibuprofen Conjugate

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