Elastin-like polypeptides (ELPs) are thermoresponsive biopolymers that undergo an LCST-like phase transition in aqueous solutions. The temperature of this LCST-like transition, T t , can be tuned by varying the number of repeat units in the ELP, sequence and composition of the repeat units, the solution conditions, and via conjugation to other biomacromolecules. In this study, we show how and why the choice of guest (X) residue in the VPGXG pentad repeat tunes the T t of short ELPs, (VPGXG) 4 , in the free state and when conjugated to collagen-like peptides (CLPs). In experiments, the (VPGWG) 4 chain (in short, WWWW) has a T t < 278 K, while (VPGFG) 4 or FFFF has a T t > 353 K in both free ELP and ELP−CLP systems. The T t for the FWWF ELP sequence decreases from being >353 K for free ELP to <278 K for the corresponding ELP−CLP system. The decrease in T t upon conjugation to CLP has been shown to be due to the crowding of ELP chains that decreases the entropic loss upon ELP aggregation. Even though the net hydrophobicity of ELP has been reasoned to drive the T t , the origins of lower T t of WWWW compared to FFFF are unclear, as there is disagreement in hydrophobicity scales in how phenylalanine (F) compares to tryptophan (W). Motivated by these experimental observations, we use a combination of atomistic and coarse-grained (CG) molecular dynamics simulations. Atomistic simulations of free and tethered ELPs show that WWWW are more prone to acquire β-turn structures than FFFF at lower temperatures. Also, the atomistically informed CG simulations show that the increased local stiffness in W than F due to the bulkier side chain in W compared to F, alone does not cause the shift in the transition of WWWW versus FFFF. The experimentally observed lower T t of WWWW than FFFF is achieved in CG simulations only when the CG model incorporates both the atomistically informed local stiffness and stronger effective attractions localized at the W position versus the F position. The effective interactions localized at the guest residue in the CG model is guided by our atomistically observed increased propensity for β-turn structure in WWWW versus FFFF and by past experimental work of Urry et al. quantifying hydrophobic differences through enthalpy of association for W versus F.

Dissipative particle dynamics simulations are applied to investigate co-micellization behavior for binary mixtures of Poloxamers in dilute aqueous solution. In view of block length similarity/dissimilarity, four representative mixture cases are considered: F127/P123, F127/P105, P123/P84, and F127/L64. With appropriate interaction parameters, the simulations enable us to examine the formation of micelles, their types, size, shape, and composition. In the investigated concentration range, we find that pure and mixed micelles, both ellipsoidal, always coexist for all cases. At similar concentrations, both species form pure micelles of their own together with mixed micelles. In the case of F127/L64, it is found that the L64 chains are involved in the mixed micelles, even when the L64 concentration is below its CMC. The fraction of L64 involved in the mixed micelles is lower as compared to the other systems studied. For all cases, the proportion of mixed micelles can be increased when the two polymer species have similar concentrations. Moreover, shorter chains may prefer to straddle the core and corona in the region of ellipsoidal interface that is closer to the center of mixed micelle.

In this work, free convective heat transfer from a horizontal cylinder immersed in quiescent power-law fluids has been investigated numerically in the laminar flow regime. The governing differential equations (continuity, momentum, and energy) have been solved over the following ranges of conditions: Grashof number, 10 ≤ Gr ≤ 105; power-law index, 0.3 ≤ n ≤ 1.8; Prandtl number, 0.72 ≤ Pr ≤ 100. The flow and heat transfer characteristics have been visualized in terms of streamlines and isotherm contours which help delineate the regions of high/low temperature. As expected, the value of the local Nusselt number decreases from its maximum value at the front stagnation point along the surface of cylinder, as the flow remains attached to the surface of the cylinder over the range of conditions covered in this study. Finally, the surface-averaged Nusselt number shows positive dependence on both Grashof and Prandtl numbers. All else being equal, shear-thinning behavior enhances the rate of heat transfer with reference to its value in Newtonian fluids. Shear-thickening behavior, however, has an adverse influence on heat transfer. The paper is concluded by presenting comparisons with the previous approximate analysis and scant experimental data available in the literature.

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Chain-exchange kinetics strongly depends on polymer concentration, its compatibility with the solvent, temperature, etc. [6][7][8] An early theory for micelles of amphiphilic molecules [9] states that their relaxation involves: (1) a fast process associated with the quick exchange of single polymer chains between the micelles and the surrounding bulk phase, and (2) a slow process for the micelle fission/ fusion process. Halperin and Alexander [10] showed that the unimer expulsion/insertion has the lowest activation energy, while micelle fusion and fission are not favored either energetically or entropically. [10,11] They deduced a scaling law for the fast relaxation process using Kramer's rate theory, and described the relaxation kinetics by a single exponential decay function. It should be noted that these theoretical studies are based on the assumption of very long core or corona forming blocks, and do not take into account the dependence of the micelle size distribution and aggregation number on the corona-forming block length.A number of experimental studies found that the chain-exchange kinetics can be fitted by a doubleexponential function [6][7][8]12,13] and the phenomenon were attributed to micellar fusion/fission along with unimer expulsion/insertion though there was no conclusive evidence. These studies of system dynamics used Dissipative particle dynamics simulation is employed to study the chain exchange kinetics between micelles of diblock copolymer in aqueous solution via in silico hybridization method. One focus is placed on the effect of chain flexibility on the dynamic behavior by varying the spring constant in the bead-spring model. The length ratio of hydrophilic to hydrophobic block is also varied. It is found that chain expulsion/insertion is the dominant mechanism in the chain exchange process. The most interesting finding is the multimodal relaxation behavior for the chain exchange and expulsion when the spring constant is small or the length ratio of hydrophilic to hydrophobic block is large. This phenomenon is due to an increase in size polydispersity of micelles with rising population of small aggregates/micelles, for which the exchange kinetics is faster. Micelles with larger aggregation numbers (>10) are found to follow single exponential relaxation kinetics.

Chain architecture is known to control macromolecular self-assembly and furthermore affect in a more complex way nanostructure stability. Equilibrium properties and chain exchange kinetics between micelles formed by tadpole-shaped diblock copolymers containing a loop-shaped hydrophobic block and a linear hydrophilic block are investigated using dissipative particle dynamics simulations. We found that tadpoles form micelles of smaller size and aggregation number than the corresponding linear diblock copolymers and have faster chain exchange kinetics, demonstrating that chain architecture can alter its effective hydrophobicity. Similar observations are made for linear diblock copolymer with a less hydrophobic core block indicating that the more compact conformation of tadpole coreforming block makes it "less hydrophobic". We show that tadpole and linear block copolymers form mixed micelles with tadpoles (or less hydrophobic chains) located on the periphery of the micelle core. The chain exchange kinetics between mixed micelles is found to be quicker than in linear diblock copolymer micelles and slower than in tadpole micelles. Tadpole escape or less hydrophobic chain exchange between mixed micelles occurs slower (in part due to the shielding role that these chains play) than in the corresponding pure micelles, while linear more hydrophobic chain exchange only slightly changes, suggesting that the exchange kinetics of the individual components can be affected differently by mixing.

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We present a simple, bottom up method for the structural design of solid microparticles containing crystalline drug and excipient using microfluidic droplet-based processing. In a model system comprising 5-methyl-2-[(2-nitrophenyl)­amino]-3-thiophenecarbonitrile (ROY) as the drug and ethyl cellulose (EC) as the excipient, we demonstrate a diversity of particle structures, with exquisite control over the structural outcome at the single-particle level. Within microfluidic droplets containing drug and excipient, tuning droplet composition and solvent removal rates allows us to controllably access structural diversity via an interplay of three physical processes (liquid–liquid phase separation, drug crystallization, and polymer vitrification) occurring during solvent removal. Specifically, we demonstrate two levels of structural controla coarse “macro” particle structure and a finer “micro” structure. Further, we elucidate the key mechanistic elements responsible for the observed structural diversity using a combination of systematic experiments, thermodynamic arguments based on a three-component phase diagram, and dissipative particle dynamics simulations. We validate our method with two different excipient and drug combinationsROY and poly­(lactic-co-glycolic acid), and EC and carbamazepine (CBZ). Finally, we present preliminary investigations of in vitro drug release from two different types of CBZ–EC particles, highlighting how structural control allows the design of drug release profiles.