scholarly journals Clinical developments of antitumor polymer therapeutics

RSC Advances ◽  
2019 ◽  
Vol 9 (43) ◽  
pp. 24699-24721 ◽  
Author(s):  
Shazia Parveen ◽  
Farukh Arjmand ◽  
Sartaj Tabassum
Keyword(s):  
Polymer Therapeutics ◽  
Drug Conjugates ◽  
Antitumor Compounds ◽  
Polymer Drug Conjugates ◽  
Drug Scaffolds

Polymer therapeutics encompasses polymer–drug conjugates that are nano-sized, multicomponent constructs already in the clinic as antitumor compounds, either as single agents or in combination with other organic drug scaffolds.

scholarly journals A tutorial translation of the description of the historically first polymer drug conjugate and its in vivo evaluation

2020 ◽  
Vol 75 (9-10) ◽  
pp. 303-311
Author(s):  
Robert Luxenhofer
Keyword(s):  
Scientific Community ◽  
World Wide ◽  
Clinical Success ◽  
German Language ◽  
In Vivo Evaluation ◽  
Polymer Therapeutics ◽  
Drug Conjugates ◽  
To Receive ◽  
Polymer Drug Conjugates

PreamblePolymer-drug conjugates have been intensively investigated for several decades, and even though their clinical success still lags behind the promise many researchers have placed in them, they are a mainstay in the fields of polymer therapeutics or nanomedicine. For many in the field, the seminal perspective paper by Helmut Ringsdorf from 1975 marks the beginning of this field of research. With more than one thousand citations, this paper has indubitably affected and inspired generations of researchers in the field, including the author of this translation. However, it is not the first paper describing the concept of polymer-drug conjugates. Some twenty years earlier, Horst Jatzkewitz described in two outstanding articles probably the historically first polymer-drug conjugates, detailed its synthesis, characterization and even first in vivo experiments. The results, carefully re-interpreted through the eyes of a scientist of the 21st century, clearly highlight several issues that need to be taken into consideration when designing polymer-drug conjugates. However, despite the pioneering nature of this paper, it is all but forgotten by the scientific community. In the author’s opinion, Horst Jatzkewitz and these papers clearly did not receive the attention and praise they deserve. Whether this was because these paper were much ahead of it´s time, or because it was published in German language, or for some other reason, we cannot know. However, these papers are, in my opinion, an excellent piece of work that should be known more widely and available to students and experts world-wide, which is why the author decided to translate it. Also, to give some more context and to help understand some outdated terms or concepts, additional comments and explanations are added throughout. I hope that this will help for these papers to receive the attention I believe they deserve.

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.

Long-Circulating and Passively Tumor-Targeted Polymer-Drug Conjugates Improve the Efficacy and Reduce the Toxicity of Radiochemotherapy

2010 ◽  
Vol 12 (9) ◽  
pp. B413-B421 ◽  
Author(s):  
Twan Lammers ◽  
Vladimir Subr ◽  
Karel Ulbrich ◽  
Peter Peschke ◽  
Peter E. Huber ◽  
...  
Keyword(s):  
Drug Conjugates ◽  
Polymer Drug Conjugates
Sign in / Sign up

Export Citation Format

Share Document