Ciprofloxacin-lidocaine-based hydrogel: development, characterization, and in vivo evaluation in a second-degree burn model.

The purpose of this work was to develop an effective carbomer hydrogel to be used to treat second-degree burns that combined ciprofloxacin and lidocaine (CbCipLid hydrogel). Its antibiotic and anesthetic efficacy and the physical and chemical properties of the CbCipLid hydrogel (release rate and kinetics, rheology, appearance, and drug content) were evaluated both before and after a sterilization cycle and also after 6 months of storage. For the in vivo studies, second-degree burns were developed in a rat model. Animals were divided into three groups: CbCipLid hydrogel, silver sulfadiazine cream (reference), and carbomer hydrogel (as control). The treatments were applied daily for 21 days, and the healing was monitored by macroscopic observation and histologic evaluation. The anesthetic effect was evaluated through the corneal touch threshold in a rabbit eye model. The CbCipLid hydrogel obtained is transparent and allows the loading of ciprofloxacin above its solubility at a neutral pH, with a rheology which is convenient for topical administration. Its physical and chemical properties remained unchanged after sterilization and for at least six additional months. Both ciprofloxacin and lidocaine are reversibly released from the CbCipLid hydrogel with a kinetics fitting the Higuchi model. The presence of a biologic-like fluid increased the rate of drug delivery through an ionic exchange mechanism. Treatment with the CbCipLid hydrogel decreased the wound-healing period, compared with the reference, and was associated with a greater number of fibroblasts and a faster rate of epithelialization and dermis reconstruction. These differences were assigned to the moist environment provided by the hydrogel and also to the presence of a therapeutic concentration of ciprofloxacin. Moreover, CbCipLid hydrogel provides an immediate anesthetic effect, which is significantly more intense than that of the reference. Based on these results, it is believed that the CbCipLid hydrogel could be a potential candidate in the prophylaxis/treatment of second-degree burns.

Systemic exposure, tissue distribution, and disease evolution of a high solubility ciprofloxacin-aluminum complex in a murine model of septicemia induced by salmonella enterica serotype Enteritidis.

A new pharmaceutical derivative obtained by stoichiometric complexation of ciprofloxacin (CIP) with aluminum (CIP-complex) has been investigated and reported in this study. Such product has high solubility in the gastrointestinal pH range and was successful in the development of optimized formulations while maintaining its antimicrobial potency. The systemic exposure, tissue distribution, and the disease evolution after given CIP-complex were assessed. The systemic exposure and distribution in intestines, lungs, and kidneys after a single intragastric administration of CIP-complex and CIP given alone, used as reference, were performed in Balb-C mice at a dose of 5 mg CIP/kg. For the assessment of the disease evolution assay, mice were infected with a virulent strain of Salmonella enterica serotype Enteritidis and treated intragastrically once or twice daily during 5 consecutive days with solutions of CIP-complex or the reference. Clinical follow up and survival was measured during 15 days post inoculation and health state was scored during this period from 0 to 5. CIP-complex showed a 32% increase in C(max), an earlier T(max), and a smaller AUC(0-12) than the reference. Maximum tissue concentrations (0.5-1 h) were significantly higher in CIP-complex (447% in intestine, 93% in kidney, and 44% in lungs). In the infection model used in this study, survival in CIP-complex versus CIP groups was 40% versus 20% (twice-daily administration) and 30% versus 0% (once-daily administration). Health state of the survivors of CIP-complex group (5/5) was higher than CIP group (3/5). The greater effectiveness of CIP-complex is attributed to the higher levels of CIP in the intestine. Our results supported the fact that CIP-complex is a promising candidate to develop dose-efficient formulations of CIP for oral administration.