New MultiPEG-conjugated theophylline derivatives: Synthesis and pharmacological evaluations

New Syntheses of Branched, Multifunctional High-Molecular Weight Poly(ethylene glycol)s or (MultiPEG)s

“…This in principle will allow the administration of a correspondingly lower amount of polymer of the same size, to achieve the same level of drug concentration within the body, when used as carrier for pharmacological purposes. The high molecular weight of these polymeric supports is another important feature, since a long lasting release can be observed using large size polymer derivatives [29]. Additionally, from the point of view of its synthetic applications, an increased production level for the same starting amount of the soluble, inert support can be easily envisaged.…”

Multimeric, Multifunctional Derivatives of Poly(ethylene glycol)

“…Moreover, the introduction of an urethane bond within the final polyether backbone will likely allow for more advantageous biodegradability properties in comparison with other similar branched derivatives. In fact, some hydrolysis at the level of the urethane bond [34] is expected to take place in physiological media. Also, it should be emphasized that the use of low-dispersed polymers as starting building units will also guarantee the low level of polydispersity for the larger, final MultiPEG.…”

“…This molecule is used as a bronchodilator, but, in spite of its good oral bioavailability, the rather short half-life and its narrow therapeutic range (10-20 µg/mL) in plasma make it necessary to administer the drug relatively often, while the peak levels achieved shortly after administration are associated with the observed side effects. Active theophylline molecules were covalently linked to two new multifunctional high-molecular weight poly(ethylene glycol) derivatives (MultiPEG) yielding PentaPEG 2000 - [7-(hydroxymethyl)theophylline] 12 and TetraPEG 6000 -[7-(hydroxymethyl)theophylline] 10 [34] derivatives. The drug loading was increased up to six times in comparison with commercial PEG of the same molecular weight.…”

“…The investigation of these drugs, characterized by low solubility in water and poor bioavailability, included PEGylation both on linear [44] as well as on new multimeric PEGs [34] and found that polymer conjugation could offer new advantages for the delivery and release of drugs such as an increased drug loading capability and a long lasting release. In this new approach, the two drugs have been conjugated on the same, new multifunctional MultiPEG, in a ratio which matches the usual therapeutic amounts when separately dosed.…”

Membrane surface functionalization via theophylline derivative coating and streptavidin immobilization

“…On the other hand, theophyllines are methylxantine derivatives with pharmacological applications and they have been used as templates in molecularly imprinting polymers (MIPs) related research [15]. The biological effect of theophyllines is associated to its affinity with a family of adenosine receptors known as A 1 , A 2A , A 2B , and A 3 [16].…”