Browsing by Author "Veiga, Francisco J.B."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Effect of cyclodextrins and pH on the permeation of tetracaine: supramolecular assemblies and release behaviorPublication . Teixeira, Raquel S.; Veiga, Francisco J.B.; Oliveira, Rita; Jones, Stuart A.; Silva, Sérgio M.C.; Carvalho, Rui A.; Valente, Artur J.M.This work provides a new insight on fundamental principles of the interaction mechanism between two forms of tetracaine – a potent local anesthetic – both in neutral (TC) and ionized (TC+) states, with beta- (b-CD) and hydroxypropyl-beta-cyclodextrin (HP-b-CD), and how such interactions affect the transport of tetracaine, at different concentrations, across a model membrane. The kinetics and mechanism of TC release from HPMC gels is also evaluated giving an insight on the role of cyclodextrin on the tetracaine transport. HPLC, fluorescence and NMR spectroscopies provided solid physicochemical knowledge of these systems and in vitro studies were performed to obtain relevant data on the transport and mechanism parameters. HPLC and fluorescence spectroscopy data revealed that tetracaine interacts with both cyclodextrins on a 1:1 stoichiometry but it is observed that neutral tetracaine forms more stables complexes (ca. 1050 M 1 for both cyclodextrins) than in its ionized form (628 and 337 M 1 for b-CD and HP-b-CD respectively). Despite of that, no host–guest interactions take place as seen by ROESY. This study clearly demonstrates that both forms of tetracaine are successfully released from the formulations at a controlled rate, following a Super-Case transport mechanism and the transport of tetracaine can be tuned by using cyclodextrins.
- Lysine-based surfactants as chemical permeation enhancers for dermal delivery of local anestheticsPublication . Teixeira, Raquel S.; Cova, Tânia F.G.G.; Silva, Sérgio M.C.; Oliveira, Rita; Araújo, Maria J.; Marques, Eduardo F.; Pais, Alberto A.C.C.; Veiga, Francisco J.B.The aim of this study is to investigate the efficacy of new, biocompatible, lysine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine hydrochloride, topically administered. Results show that this class of surfactants strongly influences permeation, especially in the case of the hydrophilic and ionized drug, ropivacaine hydrochloride, that is not easily administered through the stratum corneum. It is also seen that the selected permeation enhancers do not have significant deleterious effects on the skin structure. A cytotoxicity profile for each compound was established from cytotoxicity studies. Molecular dynamics simulation results provided a rationale for the experimental observations, introducing a mechanistic view of the action of the surfactants molecules upon lipid membranes.
- Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: a comprehensive study on structure–activity relationships, molecular dynamics and dermal deliveryPublication . Teixeira, Raquel S.; Cova, Tânia F.G.G.; Silva, Sérgio M.C.; Oliveira, Rita; do Vale, M. Luísa C.; Marques, Eduardo F.; Pais, Alberto A.C.C.; Veiga, Francisco J.B.This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations.