Development of molecularly imprinted co-polymeric devices for controlled delivery of flufenamic acid using supercritical fluid technology

• Published in: The Journal of supercritical fluids Vol. 58; no. 1; pp. 150 - 157
• Main Authors: da Silva, Mara Soares, Nobrega, Franklin L., Aguiar-Ricardo, Ana, Cabrita, Eurico J., Casimiro, Teresa
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-08-2011
• Subjects: Controlled release; Copolymers; Crosslinking; Drugs; Flufenamic acid; Mathematical analysis; Matrices; Matrix methods; Molecular imprinting; Self assembly; Supercritical carbon dioxide; Supercritical fluids; Flufenamic acid; Crosslinking; Supercritical carbon dioxide; Molecular imprinting; Controlled release
• ISSN: 0896-8446; 1872-8162
• DOI: 10.1016/j.supflu.2011.05.010

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► Development of molecularly imprinted co-polymers using supercritical fluid technology. ► scCO
2-assisted impregnation with the target drug. ► Imprinted polymers uptake higher amounts of drug than non-imprinted polymers. ► Affinity polymers have more sustained drug delivery. ► Molecular recognition can be tuned by varying operational parameters.
This work reports the development of a novel class of affinity co-polymeric materials using supercritical fluid technology. Polymeric materials with molecular recognition to flufenamic acid, were first synthesized in supercritical carbon dioxide (scCO
2) using the drug as template. Molecularly imprinted co-polymers of methacrylic acid (MAA) or
N-isopropyl acrylamide (NIPAAm) crosslinked with ethylene glycol dimethacrylate (EGDMA) were synthesized using different crosslinking degrees and template:monomer ratios, at 65
°C and 21
MPa. High-pressure NMR experiments confirmed that the nature of the interactions between the drug and the functional monomers during the polymerization step are mainly hydrogen bonds. scCO
2-assisted impregnation revealed that the imprinted matrices were able to uptake higher amounts of flufenamic acid. This effect was particularly evidenced in the more crosslinked matrices, with P(MAA–EGDMA) imprinted copolymers binding up to 101.5
mg drug/g polymer against only 50.5
mg/g in the non-imprinted copolymer.
In vitro drug delivery experiments showed that imprinted co-polymers release the drug in a more sustained way than the corresponding non-imprinted matrices. Overall it was shown that supercritical fluid technology is a viable approach for the development of self-assembly molecular recognition polymers with potential application in controlled drug delivery systems.