Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-ß-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

Guest-Mediated Reversal of the Tumbling Process in Phosphorus-Dendritic Compounds Containing ß-Cyclodextrin Units: An NMR Study.

The conformational study of dendritic platforms containing multiple ß-cyclodextrin (ßCD) units in the periphery is relevant to determine the availability of ßCD cavities for the formation of inclusion complexes in aqueous biological systems. In this work, we performed a detailed conformational analysis in D2O, via 1D and 2D NMR spectroscopy of a novel class of phosphorus dendritic compounds of the type P3N3-[O-C6H4-O-(CH2)n-ßCD]6 (where n = 3 or 4). We unambiguously demonstrated that a functionalized glucopyranose unit of at least one ßCD unit undergoes a 360° tumbling process, resulting in a deep inclusion of the spacer that binds the cyclodextrin to the phosphorus core inside the cavity, consequently limiting the availability of the inner cavities. In addition, we confirmed through NMR titrations that this tumbling phenomenon can be reversed for all ßCD host units using a high-affinity guest, namely 1-adamantanecarboxylic acid (AdCOOH). Our findings have demonstrated that it is possible to create a wide variety of multi-functional dendritic platforms.

Host-Guest Recognition of Pesticides by Calixarenes.

This article is based on a review of the literature and our own experience with toxicological molecules. We explain the nature of calix[n]arenes and as their recognized properties are used to detect compounds of toxicological interest, mainly the most important pesticide families such as organophosphorated, organochlorine compounds, pyrethroid insecticides, carbamate fungicides, and herbicides, using different techniques. In addition, we show the role of the macrocycle and its interactions, and the advantage of using this type of compound for improving conventional techniques, where the phenomenon of recognition is very important, such as chromatography, solid-phased extraction, and the development of specific sensors, among others and Even we also show the use of this macrocycle for detoxication procedures in vivo. In this way, we display as the multiple possibilities of functionalization of the calix[n]arenes makes these versatile molecules in the phenomena of specific recognition. Finally, This review highlights the main analytical methods reported in the literature for determination of plaguicides by host-guest interaction with calixarenes. In this way, among the available analytical tools, chromatographic, and electrochemical-based methods are the most used techniques for the detection and to quantify plaguicides using calixarenes.

Thermodynamic compatibility between cyclodextrin supramolecular complexes and surfactant.

Supramolecular structures based on cyclodextrins have been extensively used for drug delivery systems over decades. However, combining host and guest molecules in a pharmaceutical formulation is not a trivial process, being one of the majors concern the inclusion complex compatibility with other excipients presented in the final formulation. Herein, experimental and theoretical calculations were used to investigate the competition of sodium dodecyl sulfate (SDS) with atenolol (ATE) or losartan (LOS), antihypertensive drugs widely used in the treatment of hypertension. Our findings, using nuclear magnetic resonance and isothermal titrations calorimetry experiments and molecular dynamic simulations demonstrated that LOS remain included into CD cavity after excipient (SDS) addition, which was not verified for ATE ternary system, being the drug displaced by SDS molecule.