Drug–polymer conjugates with dynamic cloud point temperatures based on poly(2-oxazoline) copolymers

2020 ◽  
Vol 11 (32) ◽  
pp. 5191-5199
Author(s):  
Jong-Ryul Park ◽  
Mariah Sarwat ◽  
Eleonore C. L. Bolle ◽  
Melody A. de Laat ◽  
Joachim F. R. Van Guyse ◽  
...  
Keyword(s):  
Cloud Point ◽  
Ace Inhibitor ◽  
Polymer Conjugates ◽  
Drug Conjugates ◽  
Polymer Drug Conjugates

A shift in cloud point temperatures of poly(2-oxazoline)/ACE inhibitor polymer drug conjugates occurs on release of the drug.

scholarly journals Polymer conjugates with potential biological activity based on new derivatives of 2-mercaptobenzoxazole-synthesis and characterization

2013 ◽  
Vol 11 (11) ◽  
pp. 1808-1815 ◽  
Author(s):  
Rǎdiţa Aparaschivei ◽  
Valeriu Şunel ◽  
Mihaela Holban ◽  
Marcel Popa ◽  
Jacques Desbrieres
Keyword(s):  
Controlled Drug Release ◽  
Biologically Active ◽  
Synthesis And Characterization ◽  
Polymeric Support ◽  
Polymer Conjugates ◽  
Drug Conjugates ◽  
Laboratory Screening ◽  
Ft Ir ◽  
Polymer Drug Conjugates ◽  
Derivatives Of

AbstractNew potentially biologically active compounds derived from 2-mercapto-benzoxazole were synthesized and coupled on polymeric support of poly (maleic anhydride-alt-vinyl acetate) for the preparation of polymer-drug conjugates with controlled drug release. All compounds were characterized by elemental and spectroscopy (FT-IR, 1H-NMR) analysis. The toxicological tests recommend the products for further laboratory screening.

scholarly journals Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 700
Author(s):  
Alena Libánská ◽  
Eva Randárová ◽  
Franck Lager ◽  
Gilles Renault ◽  
Daniel Scherman ◽  
...  
Keyword(s):  
Near Infrared ◽  
Therapeutic Potential ◽  
Joint Inflammation ◽  
Ph Sensitive ◽  
Current Therapy ◽  
Polymer Conjugates ◽  
Drug Conjugates ◽  
Anti Inflammatory ◽  
Polymer Drug Conjugates

Polymer-drug conjugates have several advantages in controlled drug delivery to inflammation as they can accumulate and release the drug in inflamed tissues or cells, which could circumvent the shortcomings of current therapy. To improve the therapeutic potential of polymer-drug conjugates in joint inflammation, we synthesized polymer conjugates based on N-(2-hydroxypropyl) methacrylamide) copolymers labeled with a near-infrared fluorescent dye and covalently linked to the anti-inflammatory drug dexamethasone (DEX). The drug was bound to the polymer via a spacer enabling pH-sensitive drug release in conditions mimicking the environment inside inflammation-related cells. An in vivo murine model of adjuvant-induced arthritis was used to confirm the accumulation of polymer conjugates in arthritic joints, which occurred rapidly after conjugate application and remained until the end of the experiment. Several tested dosage schemes of polymer DEX-OPB conjugate showed superior anti-inflammatory efficacy. The highest therapeutic effect was obtained by repeated i.p. application of polymer conjugate (3 × 1 mg/kg of DEX eq.), which led to a reduction in the severity of inflammation in the ankle by more than 90%, compared to 40% in mice treated with free DEX.

Designing polymer conjugates as lysosomotropic nanomedicines

2007 ◽  
Vol 35 (1) ◽  
pp. 56-60 ◽  
Author(s):  
R. Duncan
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Molecular Mass ◽  
Anticancer Agents ◽  
Synthetic Polymer ◽  
Water Soluble ◽  
Hpma Copolymer ◽  
Polymer Conjugates ◽  
Drug Conjugates ◽  
Polymer Drug Conjugates

Marriage of cell biology (the concept of ‘lysosomotropic drug delivery’) and the realization that water-soluble synthetic polymers might provide an ideal platform for targeted drug delivery led to the first synthetic polymer–drug conjugates that entered clinical trials as anticancer agents. Conceptually, polymer conjugates share many features with other macromolecular drugs, but they have the added advantage of the versatility of synthetic chemistry that allows tailoring of molecular mass and addition of biomimetic features. Conjugate characteristics must be optimized carefully to ensure that the polymeric carrier is biocompatible and that the polymer molecular mass enables tumour-selective targeting followed by endocytic internalization. The polymer–drug linker must be stable in transit, but be degraded at an optimal rate intracellularly to liberate active drug. Our early studies designed two HPMA [N-(2-hydroxypropyl)methacrylamide] copolymer conjugates containing doxorubicin that became the first synthetic polymer–drug conjugates to be tested in phase I/II clinical trials. Since, a further four HPMA copolymer–anticancer drug conjugates (most recently polymer platinates) and the first polymer-based γ-camera imaging agents followed. Polymer–drug linkers cleaved by lysosomal thiol-dependent proteases and the reduced pH of endosomes and lysosomes have been used widely to facilitate drug liberation. It is becoming clear that inappropriate trafficking and/or malfunction of enzymatic activation can lead to new mechanisms of clinical resistance. Recent studies have described HPMA copolymer conjugates carrying a combination of both endocrine and chemotherapy that are markedly more active than individual conjugates carrying a single drug. Moreover, current research is investigating novel dendritic polymer architectures and novel biodegradable polymers as drug carriers that will provide improved drug delivery and imaging probes in the future. The present paper reviews the clinical status of polymeric anticancer agents, the rationale for the design of polymer therapeutics and discusses the benefits and challenges of lysosomotropic delivery.

scholarly journals Polymer-Drug Conjugates in Inflammation Treatment

2018 ◽  
pp. S281-S292 ◽  
Author(s):  
E. KOZIOLOVÁ ◽  
K. VENCLÍKOVÁ ◽  
T. ETRYCH
Keyword(s):  
Multiple Sclerosis ◽  
Lupus Erythematosus ◽  
Defense Mechanism ◽  
Water Soluble ◽  
Active Targeting ◽  
Water Soluble Polymer ◽  
Polymer Backbone ◽  
Polymer Conjugates ◽  
Drug Conjugates ◽  
Polymer Drug Conjugates

Inflammation is a vital defense mechanism of living organisms. However, persistent and chronic inflammation may lead to severe pathological processes and evolve into various chronic inflammatory diseases (CID), e.g. rheumatoid arthritis, multiple sclerosis, multiple sclerosis, systemic lupus erythematosus or inflammatory bowel diseases, or certain types of cancer. Their current treatment usually does not lead to complete remission. The application of nanotherapeutics may significantly improve CID treatment, since their accumulation in inflamed tissues has been described and is referred to as extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS). Among nanotherapeutics, water-soluble polymer-drug conjugates may be highly advantageous in CID treatment due to the possibility of their passive and active targeting to the inflammation site and controlled release of active agents once there. The polymer-drug conjugate consists of a hydrophilic biocompatible polymer backbone along which the drug molecules are covalently attached via a biodegradable linker that enables controlled drug release. Their active targeting or bio-imaging can be achieved by introducing the cell-specific targeting moiety or imaging agents into the polymer conjugate. Here, we review the relationship between polymer conjugates and inflammation, including the benefits of the application of polymer conjugates in inflammation treatment, the anti-inflammatory activity of polymer drug conjugates and potential polymer-promoted inflammation and immunogenicity.

Paclitaxel-albumin interaction in view of molecular engineering of polymer-drug conjugates

2009 ◽  
Vol 81 (3) ◽  
pp. 439-450 ◽  
Author(s):  
Michael Hess ◽  
Byung-Wook Jo ◽  
Stefan Wunderlich
Keyword(s):  
Anticancer Agent ◽  
Molecular Engineering ◽  
Water Soluble ◽  
Hydrophobic Core ◽  
Water Soluble Polymer ◽  
Polymer Conjugates ◽  
Drug Conjugates ◽  
Model Protein ◽  
Polymer Drug Conjugates ◽  
Kinetics Of

The interaction of water-soluble polymer conjugates of the anticancer agent paclitaxel and albumin as model protein has been investigated using fluorescence spectroscopy and NMR. Drugs and drug conjugates can enter the hydrophobic core of albumin; the kinetics of the interaction with the fluorophore, however, differs. Given the information about the steric situation of the formed complexes, some aspects of molecular engineering of the drug are discussed.

Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery

2020 ◽  
Vol 20 ◽  
Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Tilak R. Bhardwaj ◽  
Rajesh K. Singh
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Drug Release ◽  
Anticancer Agents ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Specific Treatment ◽  
Drug Conjugates ◽  
Polymer Drug Conjugates

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.

scholarly journals Folic Acid-Targeted Paclitaxel-Polymer Conjugates Exert Selective Cytotoxicity and Modulate Invasiveness of Colon Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 929
Author(s):  
Antonella Grigoletto ◽  
Gabriele Martinez ◽  
Daniela Gabbia ◽  
Tommaso Tedeschini ◽  
Michela Scaffidi ◽  
...  
Keyword(s):  
Folic Acid ◽  
Cancer Cells ◽  
Pharmacokinetic Profile ◽  
Strong Impact ◽  
Passive Targeting ◽  
Drug Conjugates ◽  
Tumor Delivery ◽  
The Right ◽  
Polymer Drug Conjugates ◽  
Ht 29

Although selective tumor delivery of anticancer drugs has been sought by exploiting either passive targeting or by ligand-mediated targeting, a selective anticancer therapy remains an unmet medical need. Despite the advances which have been achieved by nanomedicines, nanosystems such as polymer-drug conjugates still miss the goal of clinical efficacy. In this study, we demonstrated that polymer-drug conjugates require a thoroughly chemical design and the right targeting agent/polymer ratio to be selective and effective towards cancer cells. In particular, two PEG conjugates carrying paclitaxel and targeted with different folic acid (FA)/PEG ratios (one or three) were investigated. The cytotoxicity study in positive (HT-29) and negative (HCT-15) FA receptor (FR)-cell lines demonstrated that the conjugates with one or three FAs were 4- or 28-fold more active in HT-29 cells, respectively. The higher activity of the 3-FA conjugate was confirmed by its strong impact on cell cycle arrest. Furthermore, FA targeting had a clear effect on migration and invasiveness of HT-29 cells, which were significantly reduced by both conjugates. Interestingly, the 3-FA conjugate showed also an improved pharmacokinetic profile in mice. The results of this study indicate that thorough investigations are needed to optimize and tune drug delivery and achieve the desired selectivity and activity towards cancer cells.

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