Effect of Polymer Chain Length on the Physical Stability of Amorphous Drug-Polymer Blends at Ambient Pressure.

Rational selection of polymers for amorphous drug stabilization is necessary for further successful development of solid dispersion technology. In this paper, we investigate the effect of polymer chain length on the inhibition of amorphous drug recrystallization. To consider this problem, we prepared a drug-polymer blend (in 10:1 drug to polymer ratio) containing bicalutamide (BIC) and polyvinylpyrrolidone (PVP) with different chain lengths K10, K30, and K90. We applied broadband dielectric spectroscopy to compare the molecular dynamics of investigated samples and thoroughly recognize their crystallization tendencies from supercooled liquid state. Despite the lack of differences in molecular dynamics, we noticed significant changes in their crystallization rates. To rationalize such behavior, we performed positron annihilation lifetime spectroscopy measurements. The results showed that the value of free volume was the highest for blend with PVP K90, which at the same time was characterized by the greatest tendency to crystallize. We postulate that the polymer chain, depending on its length, can have different configurations in the space, leading to better or worse sample stabilization. Our results highlight how important is detailed understanding of physical properties of polymers for judicious selection of the best stabilization approach.

Poly (n-butyl cyanoacrylate) as a nanocarrier for rivastigmine transport across the blood-brain barrier in Alzheimer's disease treatment: a perspective from molecular dynamics simulations.

In this study, molecular dynamics simulations have been used to investigate the behavior of the drug rivastigmine and its carrier so-called poly (n-butyl cyanoacrylate) in the encapsulation process. Polymer modeling, and subsequently the emulsion polymerization model, were applied to analyze drug release in vitro and to justify rivastigmine transport across the blood-brain barrier (BBB) and polymer agglomeration. On the other hand, suitable polymer chain length, encapsulation method, polarity between polymer and drug structure, and finally, pattern of drug released in vitro and in vivo have been investigated to analyze the behavior of drug and polymer accurately. Maximum drug loading was determined based on the modeling of drug encapsulation and comparison of the radius of gyration of polymer (Rg) and distance between center of masses (COMs) of rivastigmine molecules and polymer in equilibrium condition (A°). With the aim of better understanding of drug release, we calculated the Flory-Huggins interaction parameter, diffusion coefficient, and intermolecular interaction energy. The results reveal that more drug molecules remain on the surface of the polymeric structure, with increasing the concentration of rivastigmine molecules from 3 up to 7, but the number of encapsulated drug molecules inside of the polymer remains constant. Also, calculated values of Gibbs free energy indicated that intramolecular interactions of the polymer chain overcome the intermolecular interactions between polymer and drug. Therefore, any extra loading of drug resulted in accumulation on the polymer surface. Graphical abstract Poly (n-butyl cyanoacrylate) containing rivastigmine molecules.

Fructan synthesis, accumulation and polymer traits. II. Fructan pools in populations of perennial ryegrass (Lolium perenne L.) with variation for water-soluble carbohydrate and candidate genes were not correlated with biosynthetic activity and demonstrated constraints to polymer chain extension.

Differences have been shown between ryegrass and fescue within the Festulolium subline introgression family for fructan synthesis, metabolism, and polymer-size traits. It is well-established that there is considerable variation for water-soluble carbohydrate and fructan content within perennial ryegrass. However there is much still to be discovered about the fructan polymer pool in this species, especially in regard to its composition and regulation. It is postulated that similar considerable variation for polymer traits may exist, providing useful polymers for biorefining applications. Seasonal effects on fructan content together with fructan synthesis and polymer-size traits have been examined in diverse perennial ryegrass material comprising contrasting plants from a perennial ryegrass F2 mapping family and from populations produced by three rounds of phenotypic selection. Relationships with copy number variation in candidate genes have been investigated. There was little evidence of any variation in fructan metabolism across this diverse germplasm under these conditions that resulted in substantial differences in the complement of fructan polymers present in leaf tissue at high water-soluble carbohydrate concentrations. The importance of fructan synthesis during fructan accumulation was unclear as fructan content and polymer characteristics in intact plants during the growing season did not reflect the capacity for de novo synthesis. However, the retention of fructan in environmental conditions favoring high sink/low source demand may be an important component of the high sugar trait and the roles of breakdown and turnover are discussed.

Fructan synthesis, accumulation, and polymer traits. I. Festulolium chromosome substitution lines.

The fructans found as storage carbohydrates in temperate forage grasses have a physiological role in regrowth and stress tolerance. They are also important for the nutritional value of fresh and preserved livestock feeds, and are potentially useful as feedstocks for biorefining. Seasonal variation in fructan content and the capacity for de novo fructan synthesis have been examined in a Festulolium monosomic substitution line family to investigate variation in the polymers produced by grasses in the ryegrass-fescue complex. There were significant differences between ryegrass and fescue. Fescue had low polymeric fructan content and a high oligomer/polymer ratio; synthesis of polymers longer than degree of polymerization 6 (DP6) from oligomers was slow. However, extension of polymer length from DP10/DP20 upward appeared to occur relatively freely, and, unlike ryegrass, fescue had a relatively even spread of polymer chain lengths above DP20. This included the presence of some very large polymers. Additionally fescue retained high concentrations of fructan, both polymeric and oligomeric, during conditions of low source/high sink demand. There were indications that major genes involved in the control of some of these traits might be located on fescue chromosome 3 opening the possibility to develop grasses optimized for specific applications.