Polymer-drug conjugates

About: Polymer-drug conjugates is a research topic. Over the lifetime, 242 publications have been published within this topic receiving 16489 citations.

The dawning era of polymer therapeutics

Abstract: As we enter the twenty-first century, research at the interface of polymer chemistry and the biomedical sciences has given rise to the first nano-sized (5-100 nm) polymer-based pharmaceuticals, the 'polymer therapeutics'. Polymer therapeutics include rationally designed macromolecular drugs, polymer-drug and polymer-protein conjugates, polymeric micelles containing covalently bound drug, and polyplexes for DNA delivery. The successful clinical application of polymer-protein conjugates, and promising clinical results arising from trials with polymer-anticancer-drug conjugates, bode well for the future design and development of the ever more sophisticated bio-nanotechnologies that are needed to realize the full potential of the post-genomic age.

Polymer conjugates as anticancer nanomedicines

Abstract: Polymers can be conjugated to anticancer drugs and proteins to improve their therapeutic index. Some such conjugates are in routine clinical use and there are exciting advances in development, such as polymer-based combination therapies.

Phase I Clinical and Pharmacokinetic Study of PK1 [N-(2-Hydroxypropyl)methacrylamide Copolymer Doxorubicin]: First Member of a New Class of Chemotherapeutic Agents—Drug-Polymer Conjugates

Abstract: PK1 comprises doxorubicin covalently bound to N -(2-hydroxypropyl)methacrylamide copolymer by a peptidyl linker. Following cellular uptake via pinocytosis, the linker is cleaved by lysosomal enzymes, allowing intratumoral drug release. Radically altered plasma and tumor pharmacokinetics, compared to free doxorubicin, and significant activity in animal tumors have been demonstrated preclinically. We aimed to determine the maximum tolerated dose, toxicity profile, and pharmacokinetics of PK1 as an i.v. infusion every 3 weeks to patients with refractory or resistant cancers. Altogether, 100 cycles were administered (range, 20–320 mg/m 2 doxorubicin-equivalent) to 36 patients (20 males and 16 females) with a mean age of 58.3 years (age range, 34–72 years). The maximum tolerated dose was 320 mg/m 2 , and the dose-limiting toxicities were febrile neutropenia and mucositis. No congestive cardiac failure was seen despite individual cumulative doses up to 1680 mg/m 2 . Other anthracycline-like toxicities were attenuated. Pharmacokinetically, PK1 has a distribution t 1/2 of 1.8 h and an elimination t 1/2 averaging 93 h. 131 I-labeled PK1 imaging suggests PK1 is taken up by some tumors. Responses (two partial and two minor responses) were seen in four patients with NSCLC, colorectal cancer, and anthracycline-resistant breast cancer. PK1 demonstrated antitumor activity in refractory cancers, no polymer-related toxicity, and proof of principle that polymer-drug conjugation decreases doxorubicin dose-limiting toxicities. The recommended Phase II dose is 280 mg/m 2 every 3 weeks. Studies are planned in colorectal, NSCLC, and breast cancer patients.