Surface activity and self-aggregation ability of three cationic quaternized aminocalix[4]arenes

The self-aggregation ability of three amphiphilic cationic calix[4]arenes possessing four quaternary amino groups (aminoCAs) was investigated using a variety of methods. All of the studied compounds possess high aggregation ability. Their critical aggregation concentration (CAC) values in water are in the 0.0009-0.04 % (w/v) concentration range. Several size populations of aggregates were detected by DLS for all three CAs, and restructuring of aggregates was observed to be dependent on concentration. Particles formed above CAC were attributed to formation of vesicular structures (vesicles). The coexistence of other type of aggregates (presumably micelles) with vesicles was observed in the aqueous solution of CAs 2 and 3 from concentrations of 0.5 and 0.8 % (w/v), respectively. The filtration procedure was found to be a significant factor since the obtained data from filtered and unfiltered samples was different. The particle sizes obtained by TEM measurements were somewhat correlated with the DLS data for unfiltered CAs solutions. An analysis of the aggregate composition was undertaken by a size-exclusion method using semi-permeable cellophane membranes with different MWCO. A negative deviation from linearity of permeability flux profile starting from 0.8 % (w/v) concentration of donor phase indicated that the fraction of large aggregates at this point is significant enough that the molecules could not easily permeate through the membranes

Antifungal drug solubilizing activity and self-aggregation ability of cationic aminocalix[4]arene in comparison to SBEβCD:effect of addition of water-soluble polymer

Ionized calixarene derivatives often possess properties of typical surfactants, aggregating in aqueous solutions. Their solubilizing properties, in this case, are often greater than conventional excipients, cyclodextrins. This in addition to their reported low toxicity makes these compounds promising pharmaceutical excipients. In this study we investigate the solubilizing ability of a cationic aminocalix[4]arene (CALIX), towards antifungal drugs, alone and with addition of HPMC. Next, the compound's self-aggregation properties in the presence of drug alone or in conjunction with polymer were studied using DLS, and compared to that for SBEβCD. Twenty percent (w/v) CALIX solution solubilizes antifungal drugs more efficiently than SBEβCD, improving for example the solubility of clotrimazole more than 21,000 times compared to its intrinsic solubility, and addition of 0.25 % HPMC into complexation media increases this effect further. Introduction of drug alone or in combination with the polymer into the complexation media significantly changes the microenvironment of excipient's aqueous solution, resulting either in smaller or larger aggregates depending on the drug chosen, presence of the polymer or the excipient used. Growth of the aggregates is observed to a greater extent upon introduction of clotrimazole into the media than with econazole nitrate and in some cases the particles were large enough to be observed by conventional light microscopy