Development and evaluation of ciprofloxacin local controlled release materials based on molecularly imprinted polymers.

The aim of this study was the molecular imprinting polymers (MIPs) assessment as a controlled release system of ciprofloxacin. The MIPs synthesis was performed by three different methods: emulsion, bulk, and co-precipitation. Lactic acid (LA) and methacrylic acid (MA) were used as functional monomers and ethylene glycol dimethacrylate as crosslinker. Also, nonimprinted polymers (NIPs) were synthesized. MIPs and NIPs were characterized by scanning electron microscopy, Fourier Transform Infrared Reflection, specific surface area, pore size, and release kinetics. Their efficiency against Staphylococcus aureus and Escherichia coli, and their cytotoxicity in dermal fibroblast cells were proven. Results show that MIPs are mesoporous materials with a pore size between 10 and 20 nm. A higher adsorption with the co-precipitation MIP with MA as a monomer was found. The release kinetics proved that a non-Fickian process occurred and that the co-precipitation MIP with LA presented the highest release rate (90.51 mg/L) in 8 h. The minimum inhibitory concentration was found between 0.031 and 0.016 mg/L for Staphylococcus aureus and between 0.004 and 0.031 mg/L for the Escherichia coli. No cytotoxicity in cellular cultures was found; also, cellular growth was favored. This study demonstrated that MIPs present promising properties for drug administration and their application in clinical practice.

P2X7 receptors contribute to the currents induced by ATP in guinea pig intestinal myenteric neurons.

The whole-cell configuration, several pharmacological tools, and single-cell RT-PCR were used to investigate the contribution of P2X7 subunits to the ATP-induced currents (I(ATP)) in guinea pig myenteric neurons. I(ATP) was recorded in the great majority of tested neurons. ATP concentration-response curve (0.01-10mM) showed two phases, the first mediated by high-sensitive P2X receptors (hsP2X receptors), observed between 0.01-0.3mM and the second mediated by low-sensitive P2X receptors (lsP2X receptors). The calculated EC(50) values of these phases were 38 and 1759 µM, respectively. 2'-3'-O-(4-benzoylbenzoyl)-ATP (BzATP) concentration-response curve was monophasic (0.01-1mM), and less potent (EC(50) 142 µM) than ATP to activate hsP2X receptors. A strong inward rectification was noticed when hsP2X receptors were activated with ATP (0.1mM) and for BzATP-induced currents (0.1mM; I(BzATP)) but a significant lower rectification was noticed when lsP2X receptors were activated (5mM). Brilliant blue G (BBG) at a concentration of 0.3 µM (known to inhibit only P2X7 receptors) reduced I(ATP) when lsP2X receptors contributed to it but neither affect hsP2X receptors nor I(BzATP). However, hsP2X receptors and I(BzATP) were both inhibited by concentrations ≥ 1 µM of this antagonist. BzATP inhibited hsP2X receptors and therefore, it behaves as partial agonist on these receptors. Using the single-cell RT-PCR technique P2X7 mRNA was detectable in 7 out of 13 myenteric neurons exhibiting P2X2 mRNA. Altogether, our results show that low-sensitive P2X receptors are likely P2X7, whereas, the high-sensitive P2X channels are probably constituted, at least in part, by P2X2 subunits.