Polymeric drugs derived from ibuprofen with improved antiinflammatory profile.
A new methacrylic monomeric compound bearing Ibuprofen (MIA) and the respective polymethacrylic macromolecular derivative (polyMIA) were evaluated for antiinflammatory properties in order to study their pharmacological activity profile. The macromolecular drug is constituted of Ibuprofen residues linked covalently to a polymethacrylic support, as a side substituent of the repeating unit, by means of a spacer group (p-aminophenoxy) that, in addition, is the most representative metabolite of Paracetamol. The Ibuprofen is slowly released from the polymeric support by hydrolysis of the ester bond in a biological medium. Different antiinflammatory testing methods were used; and the results obtained indicate that the monomeric and polymeric forms display higher potency to inhibit acute inflammatory processes than the traditional Ibuprofen form, even doubling the power of Ibuprofen. In addition, they present higher activity against chronic experimental processes, as well as an excellent antinociceptive behavior to inhibit the pain associated with arthritic diseases. According to previous reports and results presented in this article, we can conclude that the new polymethacrylic structures show higher analgesic, antipiretic, and antiinflammatory activities due to the possible activity of the macromolecular drug as well as to the controlled Ibuprofen release from the macromolecular delivery system. After releasing of the side active residue, a derivate of poly(sodium methacrylate) is formed, which is cleared from the body easily by the normal pathway of kidney metabolism.
Liso
P A
PA
Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense de Madrid, Spain.
Rebuelta
M
M
San Román
J
J
Gallardo
A
A
Villar
A M
AM
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy; D002351:Carrageenan / Q000633:toxicity; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005620:Freund's Adjuvant / Q000633:toxicity; D006868:Hydrolysis; D006930:Hyperalgesia / Q000188:drug therapy; D007052:Ibuprofen / Q000008:administration & dosage* / Q000494:pharmacology; D008689:Methacrylates / Q000008:administration & dosage*; D051379:Mice; D013535:Suspensions
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004343:Drug Implants; D008689:Methacrylates; C104743:N-(4-(2-(4-isobutylphenyl)propionyloxy)phenyl)methacrylamide; D013535:Suspensions; D002351:Carrageenan; D005620:Freund's Adjuvant; D007052:Ibuprofen