Polymer Conjugates

Abstract

Soluble polymer conjugates have only recently been introduced into clinical practice. They can be subdivided into 2 main categories: polymer-protein conjugates, so far the most widely studied; and polymer-drug conjugates, particularly those containing conventional antitumour agents, that are still at an early stage of development. Polymer conjugation can be used to alter the biodistribution, elimination and rate of metabolism of covalently bound drugs. In the case of protein adducts, polymer conjugation prolongs the protein plasma elimination half-life (5- to 500-fold increases in elimination half-life have been reported), reduces proteolytic degradation and has the added benefit of reducing immunogenicity. Cellular uptake of low molecular weight drugs convalently bound to polymeric carriers is restricted to the endocytic route. Thus, the organ and subcellular distribution of the drug can be modified. Cellular uptake has been used to facilitate drug targeting and decreased toxicity. In this review, the theoretical rationale for polymer conjugation is described, as is the limited clinical pharmacokinetic experience with polymer conjugates. As an alteration of the pharmacokinetic profile of a drug was one of the underlying arguments for creation of polymeric conjugates, more clinical pharmacokinetic studies are urgently needed to permit the validation of appropriate pharmacokinetic models that can be used in the future to assist in the optimisation of clinical protocols, and improved conjugate design.

Toxicity on Dengue Mosquito Vectors Through Myristica fragrans-Synthesized Zinc Oxide Nanorods, and Their Cytotoxic Effects on Liver Cancer Cells (HepG2)

“…However, most of the reports focused on the synthesis of Ag and Au nanoparticles. For instance, Ag nanoparticles biosynthesized using the seed extract of Moringa oleifera were highly effective against A. aegypti young instars, with LC 50 of 10.24 ppm (I), 11.81 ppm (II), 13.84 ppm (III), 16.73 ppm (IV) and 21.17 ppm (pupae) compounds [32]. Phyllanthus niruri-synthesized Ag nanoparticles were also highly effective in laboratory experiments conducted against A. aegypti larvae, with LC 50 of 3.90 ppm (I), 5.01 ppm (II), 6.2 ppm (III), 8.9 ppm (IV), and 13.04 ppm (pupae) [6].…”

“…The small nature of nanoparticles allows them to cross cellular membranes and their high surface area to volume ratio can allow increased loading of therapeutics [16].…”

Nanostructured materials for applications in drug delivery and tissue engineering

“…Polymer-drug conjugates, which contain a systemically-stable, bioresponsive polymer-drug linker, alter the pharmacokinetics of the drug by increasing the drug's effective molecular weight [21]. The linker ensures that the pro-drug remains inactive in circulation until it is specifically liberated at the target site by the appropriate enzyme or pH.…”

Protein–polymer therapeutics: a macromolecular perspective

“…11,12 Nonetheless, the selection of chemistry for the attachment of polymeric macromolecules without compromising the protein structure and activity remains a primary concern. 13,14 In this aspect, reversible modification of proteins with polymers via supramolecular interactions provides the possibility of releasing polymers from the protein core under the designated conditions. 15 Consequently, the modified protein could potentially benefit from an improved stability due to the polymer modification and regain their full bioactivity upon release.…”