Polyethylene Prodrugs Using Precisely Placed Pharmaceutical Agents

Abstract

Polyethylene‐based polymeric prodrugs have been prepared by acyclic diene metathesis (ADMET) polymerization; this condensation type, step growth polymerization, affords controlled polymer architectures via exact methylene run lengths between drug branches. Polyethylene was synthesized with the nonsteroidal anti‐inflammatory drug (NSAID) branches ibuprofen and naproxen attached at every 21st backbone carbon through a hydrolysable ester linkage. These ester linkages can have their reactivity tuned by using a variety of spacers that link the drug to the polymer backbone. Two types of spacers, tetraethylene glycol (TEG, hydrophilic) and decanediol (hydrophobic), were incorporated between the drugs and the polymer backbone to observe the effect of spacer properties on the rate of drug release. The rate of hydrolysis and subsequent release of drug was monitored as a direct effect of the spacer and type of reactive linker. With the primary structure of the polymers perfectly known, making such subtle changes to these structures has a dramatic influence on their physical properties. The polymers discussed herein are characterized with NMR, IR, TGA, and DSC. The rate at which these materials hydrolyze and release their pharmaceutical species via enzymatic or chemical hydrolysis was monitored by UV‐vis. Tailoring the type of spacer and hydrolysable linker to a particular drug offers a new class of polyethylene with controllable features that can be used in the application of a new drug delivery material.magnified image

Synthesis and Controlled Release Behavior of Biodegradable Polymers with Pendant Ibuprofen Group

“…According to the structure shown in Figure 1, the content of ibuprofen moiety in synthesized polymer carriers was calculated as 37.7% for PIGB, 35.2% for PIGH, and 35.3% for PIGA, respectively. By the polymeric drug or pendant drug methods, the drug-loading capacity was also greatly increased in some other reported systems such as malic acidbased polyester [28], poly( -caprolactone-co-lactide) [29], polyacrylic ibuprofen prodrug [17], ibuprofen carrier from polyethylene glycol [30], and polyethylene-based polymeric prodrugs [16].…”

“…The loading ratio of the drug 2 International Journal of Polymer Science is around 1-23%. In addition, the widely used materials in the drug systems are usually acrylic/vinyl polymers with C-C bond in their main-chains such as poly(methyl methacrylate/hydroxyethyl methacrylate) [12], polyethylene [16], poly(2-hydroxypropyl acrylate) [17], poly(hydroxyethyl methacrylate) [18], poly(methacrylic acid) [19], poly(Nisopropylacrylamide) [20,21], and poly(vinylpyrrolidone) [22]. These polymers are not biodegradable or biocompatible in nature.…”

ADMET: Metathesis polycondensation

“…From the most recent years, advances have centered around obtaining suitable diene monomers from renewable resources including fatty acids,80–83 carbohydrates,103 amino acid dimers,104 and even bile acid105 while probing polymer interactions more typical to biological systems 102, 106, 107. Moving toward using the well‐defined ADMET polymers in delivery applications108, 109 has also seen vast progress (Fig. 14).…”

Hybrid polymers bearing oligo-l-lysine(carboxybenzyl)s: synthesis and investigations of secondary structure

“…Acyclic diene metathesis (ADMET) polymerization [32][33][34] opens up possibilities to introduce different kinds of functional groups [35][36][37][38] into a polyethylene chain, introducing even anti-inammatory drugs, such as ibuprofen and naproxen, into a polyethylene backbone. 39 The ROP of NCA monomers is a viable and proven strategy to obtain articial homo-and block co-peptides, where end group functionalized polymers can be obtained, given that the ROP mechanism follows the aspects of "livingness". 40,41 Firstly, mono-functional oligo-L-lysine(Z)s with varying repeating units (n ¼ 3, 6, 12, 24, 30) were synthesized via ROP of the lysine-NCA monomer using 11-aminoundece as the primary initiator in DMF.…”