ABSTRACT
Aim: Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 h after an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH. Materials & methods: Wistar rats were randomly selected to receive an intravenous injection of hUC-MSC or the vehicle 1 h after a severe ICH. Results: The hyperacute treatment with hUC-MSC did not affect the 22-day survival rate, the motor function or the residual hematoma volume. Conclusion: These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH.
ABSTRACT
The recommended method for the biopharmaceutical evaluation of drug solubility is the shake flask; however, there are discrepancies reported about the solubility of certain compounds measured with this method, one of them is candesartan cilexetil. The present work aimed to elucidate the solubility of candesartan cilexetil by associating others assays such as stability determination, polymorphic characterization and in silico calculations of intrinsic solubility, ionized species, and electronic structures using quantum chemistry descriptors (frontier molecular orbitals and Fukui functions). For the complete biopharmaceutical classification, we also reviewed the permeability data available. The polymorphic form used was previously identified as the form I of candesartan cilexetil. The solubility was evaluated in biorelevant media in the pH range of 1.2-6.8 at 37.0°C according to the stability previously assessed. The solubility of candesartan cilexetil is pH dependent and the dose/solubility ratios obtained demonstrated the low solubility of the prodrug. The in silico calculations supported the found results and evidenced the main groups involved in the solvation, benzimidazole, and tetrazol-biphenyl. The human absolute bioavailability reported demonstrates that candesartan cilexetil has low permeability and when associated with the low solubility allows to classify it as class 4 of the Biopharmaceutics Classification System.
