New Acrylic Polymers for Surface Modification of Enzymes of Therapeutic Interest and for Enzyme Immobilization

Veronese, Francesco M.; Visco, C.; Massarotto, S.; Benassi, C. A.; Ferruti, Paolo

doi:10.1111/j.1749-6632.1987.tb45752.x

Cited by 8 publications

(3 citation statements)

References 6 publications

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“…Tailor-made copolymers of N-acryloylmorpholine and N-acryloxysuccinimide are prepared by radical copolymerization, the former monomer providing water solubility to the copolymer and the latter reactivity toward protein amino groups. Copolymers are successfully used to modify catalase and ribonuclease A, and the conjugates maintain full enzyme activity (168,169).…”

Section: Properties and Methods Of Activation Of Polymers For Drug Co...mentioning

confidence: 99%

Stabilization of Substances in Circulation

1998

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427 3.3. Liposomes as Drug Carriers and Their in Vivo Fate 427 3.4. Long-Circulating Liposomes 428 3.4.1. GM1 and Glucoronide Liposomes 429 3.4.2. PEG Liposomes 430 3.4.3. Other Polymers Used in the Preparation of Long-Circulating Liposomes 430 3.4.4. Active Targeted, Thermosensitive, pH-Sensitive Long-Circulating Liposomes 431 3.4.5. Long-Circulating Liposomes for Tumor Diagnosis and Cancer Chemotherapy 432 3.5. General Considerations on Substance Entrapment in Liposomes 432 4. Particles 433 4.1. Introduction 433 4.2. Microparticles 433 4.3. Properties and Methods of Preparation of Nanoparticles 433 4.4. Nanoparticles as Drug Carriers 434 4.5. Long-Circulating Nanoparticles 434 4.6. General Considerations on Substance Entrapment in Particles 435 5. Additional Strategies 436 6. Conclusions 437

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Section: Properties and Methods Of Activation Of Polymers For Drug Co...mentioning

confidence: 99%

Stabilization of Substances in Circulation

1998

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“…A safer and more effective approach beyond PEGylation is highly desirable. Since the early 1980s, a series of synthetic polymers, including poly(N-vinylpyrrolidone),[62] polyoxazoline,[63] poly(N-acryloyl morpholine),[64] poly(vinyl alcohol),[65] polyglycerol,[66] and polyzwitterions,[67, 68] have been proposed to conjugate to proteins and function in a similar way as PEG does (Polymer structures shown in Fig. 3).…”

Section: Protein Modification Beyond Pegylationmentioning

confidence: 99%

Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation

Zhang

Sun

Liu

et al. 2016

Journal of Controlled Release

524

360

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The technique of attaching the polymer polyethylene glycol (PEG), or PEGylation, has brought more than ten protein drugs into market. The surface conjugation of PEG on proteins prolongs their blood circulation time and reduces immunogenicity by increasing their hydrodynamic size and masking surface epitopes. Despite this success, an emerging body of literature highlights the presence of antibodies produced by the immune system that specifically recognize and bind to PEG (anti-PEG Abs), including both pre-existing and treatment-induced Abs. More importantly, the existence of anti-PEG Abs has been correlated with loss of therapeutic efficacy and increase in adverse effects in several clinical reports examining different PEGylated therapeutics. To better understand the nature of anti-PEG immunity, we summarize a number of clinical reports and some critical animal studies regarding pre-existing and treatment-induced anti-PEG Abs. Various anti-PEG detection methods used in different studies were provided. Several protein modification technologies beyond PEGylation were also highlighted.

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“…[2b] The negative impact of ADA on clinical outcomes has been broadly observed in many biologic drugs, including IFN‐α2, factor VIII, GM‐CSF, and anti‐TNF Abs . Another source of Abs is the material attached to a protein including poly(ethylene glycol) (PEG), poly(N‐vinylpyrrolidone), and poly(N‐acryloyl morpholine) . Conjugation of bulky hydrophilic materials to proteins is a widely adopted strategy to mitigate the immunogenicity of a protein drug by physical shielding their immunogenic epitopes.…”

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confidence: 99%

Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs

Yuan

Zhang

et al. 2018

Advanced Materials

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For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself. However, it is unclear if the improved immunologic profiles can translate to better clinical outcomes since improved immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB nanocage (PCB NC) is developed, which can physically encase proteins while keeping their structure intact. PCB NC encapsulation of uricase, a highly immunogenic enzyme, is demonstrated to eradicate all the immune responses. To bridge the gap between immunogenicity and efficacy studies, the therapeutic performance of PCB NC uricase is evaluated and compared with its PEGylated counterpart in a clinical-mimicking gouty rat model to determine any loss of efficacy evoked after five administrations.

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New Acrylic Polymers for Surface Modification of Enzymes of Therapeutic Interest and for Enzyme Immobilization

Cited by 8 publications

References 6 publications

Stabilization of Substances in Circulation

Stabilization of Substances in Circulation

Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation

Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs

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