Three optimised nanoparticles have been developed (two uncoated and one HA-coated) and their toxicity on fibroblasts and macrophages has been evaluated: experiments showed the beneficial character of HA-coating in the reduction of toxicity (IC50 raised from 0.7-0.8 mg/mL to 1.8 mg/mL) and suggested that the uncoated chitosan/TPP nanoparticles had toxic effects following internalisation rather than membrane disruption.

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Synthetic zeolites were studied in order to investigate their ability to encapsulate and to release drugs. In particular, a zeolite X and a zeolitic product obtained from a cocrystallization of zeolite X and zeolite A were examined. These materials were characterized by chemical analyses (ICP-AES), X-ray diffraction, nitrogen adsorption isotherm, scanning electron microscopy, laser diffraction, and infrared spectroscopy. Since ketoprofen was chosen as a model drug for the formulation of controlled-release dosage forms, it was encapsulated into these two types of synthetic zeolites by a soaking procedure. Drug-loaded matrices were then characterized for entrapped drug amount and thermogravimetric behavior. In both types of activated zeolites, the total amount of ketoprofen (800 mg) was encapsulated in 2 g of matrix. By using HPLC measurements, ketoprofen release studies were done at different pH conditions so as to mimick gastrointestinal fluids. The absence of release in acid conditions and a double phased release, at two different pH values (5 and 6.8), suggest that after activation these materials offer good potential for a modified release delivery system of ketoprofen.

The Cambridge Structural Database (CSD) was searched through two 3D queries based on substructures shared by well-known antagonists at the A(1) and A(3) adenosine receptors (ARs). Among the resulting 557 hits found in the CSD, we selected five compounds to purchase, synthesize, or translate synthetically into analogues better tailored to interact with the biological targets. Binding experiments using human ARs showed that four out of five tested compounds turned out to be antagonists at the A(1)AR or A(3)AR with K(i) values between 50 and 440 nM. Lead optimizations of 2-(benzimidazol-2-yl)quinoxalines (BIQs, 3) gave the best results in terms of potency and selectivity at the A(1) and A(3) ARs. Particularly, 2-(4-ethylthiobenzimidazol-2-yl)quinoxaline (3e) exhibited K(i) values at the A(1)AR, A(2A)AR, and A(3)AR of 0.5, 3440, and 955 nM, respectively, whereas 2-(4-methylbenzimidazol-2-yl)quinoxaline (3b) displayed at the same ARs K(i) values of 8000, 833, and 26 nM, respectively.

Although ketorolac is one of the most potent anti-inflammatory and analgesic drugs, its use has been strongly limited owing to the high incidence of adverse effects reported, particularly in the gastrointestinal tract. Using the prodrug approach, which allows the reduction of toxicological features of the parent drug without altering its pharmacological properties, we synthesized an orally administrable prodrug of ketorolac by means of its reversible conjugation to D-galactose (ketogal). In a single dose study, its pharmacokinetic profile was compared with that of ketorolac. Moreover, we found that this prodrug was able to maintain the anti-inflammatory and the analgesic activity of the drug without giving rise to gastric ulcer formation. Thus, these results indicate that ketogal is a highly effective and valid therapeutic alternative to ketorolac itself.