Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

Polymeric micelles of single and mixed poloxamines (Tetronic) were evaluated regarding their ability to host the antiglaucoma agent ethoxzolamide (ETOX) for topical ocular application. Three highly hydrophilic varieties of poloxamine (T908, T1107 and T1307) and a medium hydrophilic variety (T904), possessing a similar number of propylene oxide units but different contents in ethylene oxide, were chosen for the study. The critical micellar concentration and the cloud point of mixed micelles in 0.9 per cent NaCl were slightly greater than the values predicted from the additive rule, suggesting that the co-micellization is hindered. Micellar size ranged between 17 and 120 nm and it was not altered after the loading of ETOX (2.7–11.5 mg drug g^–1 poloxamine). Drug solubilization ability ranked in the order: T904 (50-fold increase in the apparent solubility) > T1107 ≅ T1307 > T908. Mixed micelles showed an intermediate capability to host ETOX but a greater physical stability, maintaining almost 100 per cent drug solubilized after 28 days. Furthermore, the different structural features of poloxamines and their combination in mixed micelles enabled the tuning of drug release profiles, sustaining the release in the 1–5 days range. These findings together with promising hen''s egg test-chorioallantoic membrane biocompatibility tests make poloxamine micelles promising nanocarriers for carbonic anhydrase inhibitors in the treatment of glaucoma.     

The compression/absorption cycle – influence of some major parameters on COP and a comparison with the compression cycleLe cycle à compression–absorption: influence de certains paramètres importants sur le COP et comparaison avec le cycle à compression

This article concerns two main studies: a parameter study and a comparison. In the parameter study, the CAHP is focused upon. Its COP sensitivity to changes in the absorber and desorber falling-film tube length, heat exchanger area distribution, and concentration change of the solution in the absorber is studied. The relative distribution between the desorber and absorber is found to have little impact on COP. The area distributed to the solution heat exchanger and the concentration change in the absorber is found to have a large impact on COP when examined separately, but when they are studied together, and with optimized concentration change for each area distribution, the total impact is low. It is shown that the falling-film tubes should be designed to be as long as possible in order to increase the COP.The comparison involves a new procedure for comparing the performance (COP) of a compression/absorption heat pump (CAHP) with that of a compression heat pump (CHP). In the procedure local heat transfer coefficients and pressure drop are taken into account. Further, the comparison is performed for various heating applications and with specified investment level. The heating applications are typically industrial or district heating cases and are chosen to study impact of three different kinds: size of the sink and source temperature change (glide), temperature lift for a given sink and source glide and temperature level for a given sink and source glide. Ammonia/water is used as working fluid in the CAHP and isobutane in the CHP. A relevant industrial design is assumed for the CHP (including an indirect economizer coupling, suction gas heat exchanger, sub-cooler and surface enhancements in evaporator and condenser), which is not the case in previous comparisons of this type. The absorber and desorber in the CAHP are modeled as vertical falling-film tube-and-shell heat exchangers. The main results for the comparison study are: (1) the COP of the CAHP is as good as that of the CHP when the sink and source glides are 10 K; (2) when the glide of the sink and source is increased to 20 K, the CAHP has a 12% better performance than the CHP; and (3) an increased temperature lift and an increased temperature level give the CAHP a relatively worse COP. Some COP-increasing design parameters to be studied further are proposed for the CAHP.     

Drug self-assembly: A phenomenon at the nanometer scale with major impact in the structure–biological properties relationship and the treatment of disease

Under water-rich conditions, small amphiphilic and hydrophobic drug molecules self-assemble into supramolecular nanostructures. Thus, substantial modifications in their interaction with cellular structures and the ability to reach intracellular targets could happen. Additionally, drug aggregates could be more toxic than the non-aggregated counterparts, or vice versa. Moreover, since self-aggregation reduces the number of effective “monomeric” molecules that interact with the target, the drug potency could be underestimated. In other cases, the activity could be ascribed to the non-aggregated molecule while it stems from its aggregates. Thus, drug self-assembly could mislead from drug throughput screening assays to advanced preclinical and clinical trials. Finally, aggregates could serve as crystallization nuclei. The impact that this phenomenon has on the biological performance of active compounds, the inconsistent and often controversial nature of the published data and the need for recommendations/guidelines as preamble of more harmonized research protocols to characterize drug self-aggregation were main motivations for this review. First, the key molecular and environmental parameters governing drug self-aggregation, the main drug families for which this phenomenon and the methods used for its characterization are described. Then, promising nanotechnology platforms investigated to prevent/control it towards a more efficient drug development process are briefly discussed.