Macromolecular Prodrugs of Ribavirin: Concerted Efforts of the Carrier and the Drug

Smith, Anders; Wohl, Benjamin M.; Kryger, Mille B. L.; Hedemann, Natasha; Guerrero‐Sánchez, Carlos; Postma, Almar; Zelikin, Alexander N.

doi:10.1002/adhm.201300637

Cited by 24 publications

(24 citation statements)

References 27 publications

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“…The nature of the polymer carrier, its average molar mass and drug loading may each play a decisive role in the overall success or failure of the formulation. 13 In this work, we use a polymer with extensive characterization in biomedicine including advanced clinical trials, namely poly( N -(2-hydroxypropyl) methacrylamide), PHPMA. 11 For an accelerated screen of the structure–function parameter space, we obtained a library of polymers with independently varied molar mass and content of RBV.…”

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confidence: 99%

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

et al. 2015

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Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

et al. 2015

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“…In contrast, EPT strategies are poised to overcome this shortcoming and should allow nominating the drug of choice through a selection of an appropriate candidate prodrug. To investigate this for biocatalytic biomaterials, and with broader interest in hepatic drug delivery [49][50][51] and specifi cally in the treatment of hepatocellular carcinoma (HCC), we used a hepatocyte cell line (HepG2). Identical β-Glu functionalized hydrogels were used as substrates for cell culture and three different prodrugs were used to elicit the same therapeutic response, i.e.…”

Section: Choice Of the Prodrug Defi Nes The Active Ingredientmentioning

confidence: 99%

Enzyme Prodrug Therapy Engineered into Biomaterials

Mendes

Zelikin

2014

Adv Funct Materials

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In this work, enzyme-prodrug therapy (EPT) is engineered into hydrogel biomaterials to achieve localized synthesis of the drugs and their delivery to the adhering cells. The use of EPT in the context of drug delivery mediated by biomaterials signifi cantly empowers the latter in that the same hydrogel is used to successfully synthesize several drugs with dissimilar structures and therapeutic effects. The concentration of the synthesized drugs is conveniently controlled by the concentration of the administered prodrugs. Using prodrugs for two therapeutic agents allows their synthesis and delivery with independent control over the concentration and the time of administration of each of the drugs. Using these tools, sequential delivery of drugs for anti-infl ammatory and anti-proliferative activity is accomplished whereby the synthesis of drugs is mediated by the same enzyme-functionalized hydrogel. The use of EPT to perform combination therapy mediated by an implantable biomaterial is also reported. Taken together, these results contribute signifi cantly to the development of fl exible and highly powerful tools of substrate-mediated drug delivery with applications in the design of therapeutic implants and tissue engineering.

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“…micelle formation, enzymatic degradability, drug release, etc.) of prodrugs themselves [38, 39]. There is limited information about their anti-tumor activity and delivery function as prodrug carriers in vitro and in vivo .…”

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confidence: 99%

A prodrug micellar carrier assembled from polymers with pendant farnesyl thiosalicylic acid moieties for improved delivery of paclitaxel

Sun

Chen

et al. 2016

Acta Biomaterialia

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In order to achieve enhanced and synergistic delivery of paclitaxel (PTX), a hydrophobic anticancer agent, two novel prodrug copolymers, POEG15-b-PFTS6 and POEG15-b-PFTS16 composed of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks, were synthesized. Both POEG-b-PFTS polymers were able to form micelles with intrinsic antitumor activity in vitro and in vivo. Employing these micelles as a carrier to load PTX, their drug loading capacity, stability, in vivo biodistribution and tumor inhibition effect were evaluated. PTX/POEG15-b-PFTS16 mixed micelles exhibited an excellent stability of 9 days at 4°C with a PTX loading capacity of 8.2%, which was more effective than PTX/POEG15-b-PFTS6 mixed micelles. In vivo biodistribution data showed that DiR-loaded POEG-b-PFTS micelles were more effectively localized in the tumor than in other organs. Moreover, both PTX/POEG-b-PFTS micelles showed significantly higher antitumor activity than Taxol in a 4T1.2 murine breast tumor model, and the tumor inhibition and animal survival followed the order of PTX/POEG15-b-PFTS16 > PTX/POEG15-b-PFTS6 > POEG15-b-PFTS16 > Taxol ≈ POEG15-b-PFTS6. Our data suggest that POEG-b-PFTS micelles are a promising anticancer drug carrier that warrants more studies in the future.

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Macromolecular Prodrugs of Ribavirin: Concerted Efforts of the Carrier and the Drug

Cited by 24 publications

References 27 publications

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

Enzyme Prodrug Therapy Engineered into Biomaterials

A prodrug micellar carrier assembled from polymers with pendant farnesyl thiosalicylic acid moieties for improved delivery of paclitaxel

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