Complex Self-Assembly of Reverse Poly(butylene oxide)-Poly(ethylene oxide)-Poly(butylene oxide) Triblock Copolymers with Long Hydrophobic and Extremely Lengthy Hydrophilic Blocks

Abstract

Amphiphilic block copolymers have emerged during last years as a fascinating substrate material to develop micellar nanocontainers able to solubilize, protect, transport, and release under external or internal stimuli different classes of cargos to diseased cells or tissues. However, this class of materials can also induce biologically relevant actions, which complement the therapeutic activity of their cargo molecules through their mutual interactions with biologically relevant entities (cellular membranes, proteins, organelles...); these interactions at the same time, are regulated by the nature, conformation, and state of the copolymeric chains. For these reasons, in this paper we investigated the self-assembly process and physico-chemcial properties of two reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers, BO14EO378BO14 and BO21EO385BO21, which have been recently found to be very useful as drug delivery nanovehicles and biological response modifiers under certain conditions (A. Cambón et al. Int. J. Pharm. 2013, 445, 47-57) in order to obtain a clear picture of the solution behavior of this class or block copolymers and to understand their biological activity. These block copolymers are characterized by possessing long BO blocks and extremely lengthy central EO ones, which provide them with a rich rheological behavior characterized by the formation of flowerlike micelles with sizes ranging from 20 to 40 nm in aqueous solution and the presence of intermicellar bridging even at low copolymers concentrations as denoted by atomic force microscopy. Bridging is also clearly observed by analyzing the rheological response of these block copolymers both storage and loss moduli upon changes on time, temperature, and or concentration. Strikingly, the relatively wide Poisson distribution of the polymeric chains make the present copolymers behave rather distinctly to conventional associative thickeners. The observed rich rheological behavior and their tunability also make these copolymers promising materials to configure drug gelling depots.

Micellar self-assembly, bridging and gelling behaviour of two reverse triblock poly(butylene oxide)–poly(ethylene oxide)–poly(butylene oxide) copolymers with lengthy hydrophilic blocks

“…7 show a wide variety of characteristics from purely viscous to highly elastic uids. The observed behaviours seems to conrm the formation of a dynamic network for both copolymers, but specially for BO 20 EO 411 BO 20 , which becomes more and more robust as the concentration is increased, as observed for other BO m EO n BO m copolymers with very lengthy EO blocks as BO 12 27 The existence of slow relaxation processes as the copolymer concentration increases also seems to corroborate this point. For BO 8 EO 90 BO 8 micelle packing as effective hard spheres in the gel phase becomes the predominant response at much lower concentrations than for copolymer BO 20 EO 411 BO 20 , which agrees with that previously mentioned.…”

Structural Investigation of Diol and Triol Poly(oxypropylene)‐Poly(oxyethylene) Block Copolymers Micelles: Composition Dependence, Temperature Response and Clouding Behavior

“…The CP, in 25 dB, increases with concentration above 50%. The control of the sizes and viscosity is important in the production of structures for drug delivery (Cambon et al, 2014). 25 dB narrows the CP temperature range, favoring the quality control of the polyether glycol, in a way of certify its composition (Schönfeldt, 1969).…”

“…The structure used for drug delivery depends on the carried species and on the different administration, that might be, for example, parenteral (micelles), oral (micellar clusters), or subdermal and topical administration (gel depots) (Cambon et al, 2014). The performance of drug solubility and delivery by micelles depends directly on the micelle sizes, size of hydrophobic cores, and the compatibility of hydrophobic drugs with the hydrophobic segments.…”

“…The behavior of the polyether glycols in selective solvent, primarily in polar aqueous solutions, has been an important subject in fundamental and applied research (Cambon et al, 2014; Etampawala et al, 2016; Liu et al, 1997a; Parekh et al, 2012; Wang and Feng, 2010). Yet, one of the most remarkable characteristics of polyether glycols is their lower critical solution temperature (LCST) behavior in polar selective solvents, commonly referred to as cloud point (CP).…”

Polymeric lipid vesicles with pH-responsive turning on–off membrane for programed delivery of insulin in GI tract

“…a-TPS aggregate to form a membrane via hydrophobic interaction. Attachment of hydrophobic branches to linear water soluble polymers has long been used as a means for obtaining commercial polymer additives called ''associative thickeners'' that are used to boost the viscosity of solutions and suspensions (Cambon et al, 2014). This boost is thought to occur because the associative thickener self-assembles into a transient network, with contacts between the hydrophobic branches acting as physical crosslinks.…”