Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE) and desaminotyrosyl-tyrosine (DT), and the hydrophilic component is poly(ethylene glycol) (PEG). Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide) (PLGA), which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of the amorphous phase in oriented polymersN. S. Murthy, H. Minor, C. Bednarczyk, and S. KrimmCite this: Macromolecules 1993, 26, 7, 1712–1721Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ma00059a034https://doi.org/10.1021/ma00059a034research-articleACS PublicationsRequest reuse permissionsArticle Views1443Altmetric-Citations124LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The zirconium-deuterium system in addition to α-Zr consists of three deuteride phases: γ, δ, and ε. Each phase exists over a wide range of compositions. The γ phase is tetragonal. The δ phase is cubic (CaF2-type). The ε phase is tetragonal. Its lattice constants vary with composition as it approaches stoichiometry of ZrD2. The unit cell contains 4ZrD2 with atoms in similar positions as in the δ phase. The γ phase retains its structure over long periods of time at room temperature. The δ + ε region has a finite width. The sizes of interstitial octahedral and tetrahedral voids in α-Zr are calculated and shown to be larger or smaller, respectively, than those of tetrahedral sites actually occupied by deuterium atoms in the deuterides to permit interstitial solid solution.
Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery.
Polymeric substances are ideal for the fabrication of synthetic vascular grafts due to their functionality and anatomic safety. The research presented in this study investigates the properties of poly(lactic acid) (PLA) and applies these properties to the design of a polymeric vascular graft to be used in a surgical procedure that bypasses arteries blocked by deposits of fat and cholesterol. Extrusion of PLA fibers, X-ray diffraction, and tensile strength testing established the impact of processing methods including extrusion temperature, spooling speed, annealing, and stretching on the structural and mechanical properties of PLA. Based on these trials, it was determined that thin fibers extruded at high temperatures and spooling speeds would be ideal for producing a flexible vascular graft. Computer Aided Design (CAD) programs were used to design a 3D-printable vascular graft made of both PLA and thermoplastic polyurethane (TPU).
The effect of hydration on the molecular structure of amorphous poly(d,l-lactic acid) (PDLLA) with 50:50 L-to-D ratio has been studied by combining experiments with molecular simulations. X-ray diffraction measurements revealed significant changes upon hydration in the structure functions of the copolymer. Large changes in the structure functions at ∼10 days of incubation coincided with the large increase in the water uptake from ∼1 to ∼40% and the formation of voids in the film. Computer modeling based on the recently developed TIGER2/TIGER3 mixed sampling scheme was used to interpret these changes by efficiently equilibrating both dry and hydrated models of PDLLA. Realistic models of bulk amorphous PDLLA structure were generated as demonstrated by close agreement between the calculated and the experimental structure functions. These molecular simulations were used to identify the interactions between water and the polymer at the atomic level including the change of positional order between atoms in the polymer due to hydration. Changes in the partial O–O structure functions, about 95% of which were due to water–polymer interactions, were apparent in the radial distribution functions. These changes, and somewhat smaller changes in the C–C and C–O partial structure functions, clearly demonstrated the ability of the model to capture the hydrogen-bonding interactions between water and the polymer, with the probability of water forming hydrogen bonds with the carbonyl oxygen of the ester group being about 4 times higher than with its ether oxygen.
Proteins adsorbed onto biomaterial surfaces facilitate cell-material interactions, including adhesion and migration. Of particular importance are provisional matrix components, fibrinogen (Fg) and fibronectin (Fn), which play an important role in the wound healing process. Here, to assess the potential of a series of elastomeric poly(butylene succinate) copolymers for soft tissue engineering and regenerative medicine applications, we examined the adsorption of Fg and Fn. We prepared spin-coated thin films of poly(butylene succinate) homopolymer and a series of elastomeric poly(butylene succinate) copolymers with butylene succinate (PBS, hard segment) to succinate-dimer linoleic diol units (DLS, soft segments) weight ratios of 70:30, 60:40, and 50:50. X-ray diffraction was used to assess crystallinity, while the obtained thin films were characterized using quartz crystal microbalance with dissipation monitoring (QCM-D) and atomic force microscopy (AFM). Protein adsorption was assessed using QCM-D, followed by data analysis using viscoelastic modeling. On all three copolymers, we observed robust adsorption of both key provisional matrix proteins. Importantly, for both proteins, viscoelastic modeling determined that the adlayers were 30–40 nm thick and had low shear modulus values (<25 kPa), thus indicating soft orientations (end-on for Fg) or conformations (open for Fn) of the hydrated proteins. Overall, our results are very encouraging, as they predict excellent cell adhesion and migration, key features enabling tissue integration of potential PBS-DLS scaffolds.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThree-dimensional order in magnetically oriented poly(γ-benzyl L-glutamate) filmsN. S. Murthy, E. T. Samulski, and J. R. KnoxCite this: Macromolecules 1986, 19, 3, 941–942Publication Date (Print):March 1, 1986Publication History Published online1 May 2002Published inissue 1 March 1986https://pubs.acs.org/doi/10.1021/ma00157a084https://doi.org/10.1021/ma00157a084research-articleACS PublicationsRequest reuse permissionsArticle Views83Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
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