Topical ozonated oil versus hyaluronic gel for the treatment of partial- to full-thickness second-degree burns: A prospective, comparative, single-blind, non-randomised, controlled clinical trial.

INTRODUCTION AND AIM: Several studies have demonstrated that ozonated oil is effective on cutaneous wound healing. This in vivo study has been conducted to evaluate the clinical effect of the topical application of ozonated oil for 12 weeks on second-degree skin burns. METHOD: A total of 30 patients suffering from second-degree skin burns in the phase of re-epithelisation were included in this study. Every skin burn was subdivided in two symmetrical parts. One part was treated with occlusive application of ozonated oil; the contralateral part of the lesion was treated with topical application of hyaluronic acid gel, once a day for 12 weeks. A clinical evaluation and an intra-vital video-capillaroscopy were performed on every patient at baseline, 6 and 12 weeks after. RESULTS: All treated lesions improved regardless of the treatment used. Ozonated oil was as effective as hyaluronic acid in improving erythema, tension, itching and burning sensation reported by patients, and it does not exert a specific anti-angiogenic effect compared to hyaluronic acid. However it seems more effective than hyaluronic acid in reducing post-lesional hyperpigmentation. CONCLUSION: Ozonated oil, topically applied for 12 weeks, seems to be as effective as hyaluronic acid in reducing symptoms related to skin burns, but it could be more effective in preventing the post-lesional hyperpigmentation.

Conjugation of thymopentin (TP5) with lipoamino acid residues increases the hydrolytic stability and preserves the biological activity.

Three conjugates of thymopentin (TP5), an oligopeptide derived from the thymic hormone thymopoietin, with lipoamino acid (LAAs) have been obtained by solid-phase peptide synthesis. Both linear and dendrimer structures have been prepared to achieve enhanced lipophilicity. After incubation in foetal calf serum the lipophilic conjugates showed a higher stability to hydrolysis with respect to the parent drug. In a preliminary in vitro biological assay, LAA conjugates showed the ability to retain or improve the growth inhibitory activity of the parent peptide against a human lymphoblastoid cell line. The interaction of the prepared conjugates with 1,2-L-alpha-dimiristoylphosphatidylcholine multilamellar liposomes, chosen as a biological membrane model, was studied. The higher lipophilicity of TP5 conjugates was reflected in a better penetration through phospholipid bilayers, whose thermal behaviour was altered in a concentration-dependent way. Such enhanced affinity of TP5-LAA conjugates for this membrane model could anticipate a better interaction with cell membranes and, ultimately, an improved biological activity of compounds compared with the parent pentapeptide.

[In vitro and in vivo biopharmaceutical evaluation of lorazepam commercial tablets]. / Valutazione biofarmaceutica in vitro e in vivo di compresse commerciali di lorazepam.

OBJECTIVE: Lorazepam (LZM) is a broadly used tranquillizer for the treatment of anxiety. Tavor is one of the most diffused registered drug products containing LZM. Lots of generic drug products containing LZM have been registered in Italy by several pharmaceutical groups and are present in the Italian market. Due to the wide medical prescription of products containing LZM, it seemed interesting, from a technological and biopharmaceutical point of view, to perform a comparative bioequivalence evaluation of a trade marked and generic tablet formulations containing LZM available in the Italian market. MATERIALS AND METHODS: The trial vas carried out on four preparations, including Tavor (1 mg) as reference product and three generics named A, B and C. In vitro technological parameters (dissolution, uniformity of content, uniformity of weight) and in vivo (pharmacokinetic on rabbit) studies were performed. RESULTS: All the examined brands passed technological tests according the European Pharmacopeia 5th ed. and USP25. Tavor ensures a faster dissolution behaviour than the tree generics in vitro. All the pharmacokinetic parameters were within the prescriptions of EMEA, even if the reference product showed the highest values of AUC0-infinity and of Cmax. CONCLUSIONS: Obtained results show that Tavor ensures a faster dissolution behaviour than the tree generics in vitro. Moreover, considering the pharmacokinetic data, it is possible to suppose that the generics B and C are not able to provide the same therapeutic effect as the reference product.

Synthesis and preliminary in vitro screening of lipophilic alpha, gamma-bis(amides) as potential prodrugs of methotrexate.

As part of a program aimed at studying the feasibility of amide derivatives of methotrexate (MTX) as lipophilic prodrugs, with the aims of increasing passive cellular uptake and obtaining prolonged-release agents, we describe the synthesis of five long-chain alkyl bis(amides) of MTX, from decyl- to octadecylamide, by direct transamidation to the MTX diethyl ester. Compounds were subjected to a preliminary biological screening, to assess their inhibitory activity against bovine liver dihydrofolate reductase (DHFR) and in vitro antitumor activity against human leukemia CCRF-CEM cells. As a general trend, an increase in lipophilicity led to a linear reduction of enzyme inhibition; however, the bis(decyl)amide derivative showed a good intrinsic affinity for DHFR (IC50 6.41 nM), comparable to that of MTX diethyl ester and close to that of MTX (IC50 2.90 nM). In the antitumor assay, lower homologues (C10-C14) displayed an interesting activity profile, suggesting the desirability of additional studies with these and similar compounds.