Self-Associative Behavior and Drug-Solubilizing Ability of Poloxamine (Tetronic) Block Copolymers

Abstract

The incidence of the structural features on the self-assembly of different poloxamines (the conventional sequential Tetronic 304, 901, 904, 908, 1107, 1301, and 1307; a reverse-sequential counterpart Tetronic 150R1; and a chemically modified derivative, N-methylated Tetronic 1107) was thoroughly studied in 10 mM HCl by means of pi-A isotherm, surface tension, and pyrene fluorescence measurements. The size and size distribution of the aggregates were investigated by dynamic and static light scattering, and the morphology was probed by transmission electron microscopy. The abilities of the different derivatives to solubilize the drug simvastatin were also evaluated. Poloxamines with both higher PO/EO ratio and molecular weight (T1301 and T150R1) led to micelles with larger and more hydrophobic cores, particularly adequate for hosting hydrophobic molecules and protecting the labile lactone form of simvastatin from hydrolysis. On the other hand, the hydroxy acid form of simvastatin interacted with the central ethylenediamine group under alkaline pH (T304) or when a permanent positive charge due to methylation was present. Micelles of long poloxamine molecules containing large PPO blocks (with 23-29 units, namely, T1301, T1307, and T150R1), particularly the one that also has long PEO blocks, were the most physically stable toward dilution.

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

“…The CMC values of single poloxamine systems (table 1) were in the same order of magnitude of those previously obtained in HCl 10 mM using the pyrene fluorescence technique [21]. The greater the molecular weight of the copolymer, the lower the CMC.…”

“…Transcorneal permeation studies through excised rabbit cornea indicated that non-steroidal anti-inflammatory drug formulations in polymeric micelles can enhance about twofold drug permeation compared with that of an aqueous suspension of the same concentration because the dissolution step is overcome [17]. Recent studies have demonstrated that poloxamine micelles are able to host relatively hydrophobic drugs and to increase their apparent solubility and stability [20,21]. As opposed to the linear counterparts (poloxamers) that are only thermoresponsive, poloxamines (four arms of poly(ethylene oxide)-poly(propylene oxide) connected through an ethylenediamine group) are appealing amphiphiles owing to the greater chemical versatility and dually pH-and temperature-responsive behaviour [22].…”

Phase Behavior of Reverse Poloxamers and Poloxamines in Water

“…Some authors have studied the effect of pH on the associative behavior of several Tetronics. 8,[29][30][31] . With the aim of studying the behavior of Tetronic 90R4 solutions as a function of pH and/or ionic strength, dynamic light scattering was used.…”

“…Regarding the protonation of the Tetronic amine groups, both nitrogen atoms must be charged in HCl 0.1 M. Some authors have suggested that this hinders the formation of poloxamine micelles and aggregates. 8 In direct Tetronic molecules, the central moiety containing the charged amine groups is located close to the inner hydrophobic blocks. These central portions form the core of the micelles in water solutions.…”

“…Tetronic R molecules have been scarcely studied. 7,8 Due to the recent advances in polymer Phase diagrams. The phase diagrams of the water suspensions were obtained by two different techniques: direct observation of the cloud points and dynamic light scattering.…”