Polymeric systems containing dual biologically active ions

• Published in: European journal of medicinal chemistry 2011-10, Vol.46 (10), p.4980-4991
• Main Authors: Parra-Ruiz, Francisco, Toledano, Estefanía, Fernández-Gutiérrez, Mar, Dinjaski, Nina, Prieto, María Auxiliadora, Vázquez-Lasa, Blanca, San Román, Julio
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria - drug effects; Bacterial Infections - drug therapy; Bactericide polymers; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Line; Delayed-Action Preparations - chemistry; Dual functional polymers; Medical sciences; Methacrylates - chemistry; Methylmethacrylate - chemistry; Mice; Nitric Oxide - antagonists & inhibitors; Non steroidal anti-inflammatory drugs; Pharmacology. Drug treatments; Quaternary Ammonium Compounds - chemistry; Quaternary ammonium salts
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.08.004

This paper reports the synthesis and characterization of dual functional polymerizable salts containing quaternary ammonium cations ionically linked to non steroidal anti-inflammatory drugs (NSAIDs), and their polymers and copolymeric systems obtained with acrylic monomers of different hydrophilicity, e.g. methyl methacrylate and 2-hydroxyethyl methacrylate. NSAIDs used were meclofenamic acid, ketoprofen and ibuprofen. Sustained release of the NSAID from polymeric and copolymeric samples was observed over a period of 10 days and the hydrophobic/hydrophilic character of both the polymeric system and the drug played a role in the release behaviour. The antimicrobial activity of dual functional monomeric and polymeric derivatives was confirmed against Gram-positive and Gram-negative bacteria and polymeric compounds presented higher bactericidal action than the precursory monomers. The extracts of copolymeric samples had anti-inflammatory activity in a nitric oxide inhibitory assay on RAW 264.7 cells and they produced a NO inhibition around 80% within the first seven days. Polymeric systems with dual functionality possess quaternary ammonium groups that confer antimicrobial activity, and anti-inflammatory action due to ionically linked NSAID anions. [Display omitted] ► Dual functional biologically active acrylic systems bearing quaternary ammonium salts ionically linked to non steroidal anti-inflammatory drugs (NSAIDs) have been developed. ► The systems possess antibacterial activity and the NSAID released presented anti-inflammatory activity in a nitric oxide inhibitory assay. ► The systems have potential to be used in the fabrication or modification of implant devices, in particular for application in ocular contact lenses and intraocular lenses with functionality and bioactivity.