Type I collagen-PEO fibers and non-woven fiber networks were produced by the electrospinning of a weak acid solution of purified collagen at ambient temperature and pressure. As determined by high-resolution SEM and TEM. fiber morphology was influenced by solution viscosity, conductivity, and flow rate. Uniform fibers with a diameter range of 100-150 nm were produced from a 2-wt% solution of collagen-PEO at a flow rate of 100 microl min(-1). Ultimate tensile strength and elastic modulus of the resulting non-woven fabrics was dependent upon the chosen weight ratio of the collagen-PEO blend. 1H NMR dipolar magnetization transfer analysis suggested that the superior mechanical properties, observed for collagen-PEO blends of weight ratio 1:1, were due to the maximization of intermolecular interactions between the PEO and collagen components. The process outlined herein provides a convenient, non-toxic, non-denaturing approach for the generation collagen-containing nanofibers and non-woven fabrics that have potential application in wound healing, tissue engineering, and as hemostatic agents.

No abstract

The effectiveness of photomediated cross-linking of type I collagen gels in the presence of rat aortic smooth muscle cells (RASMC) as a method to enhance gel mechanical properties while retaining native collagen triple helical structure and maintaining high cell viability was investigated. Collagen was chemically modified to incorporate an acrylate moiety. Collagen methacrylamide was cast into gels in the presence of a photoinitiator along with RASMC. The gels were cross-linked using visible light irradiation. Neither acrylate modification nor the cross-linking reaction altered collagen triple helical content. The cross-linking reaction, however, moved the denaturation temperature beyond the physiologic range. A twelve-fold increase in shear modulus was observed after cross-linking. Cell viability in the range of 70% (n = 4, p > 0.05) was observed in the photo-cross-linked gels. Moreover the cells were able to contract the cross-linked gel in a manner commensurate with that observed for natural type I collagen. Methacrylate-mediated photo-cross-linking is a facile route to improve mechanical properties of collagen gels in the presence of cells while maintaining high cell viability. This enhances the potential for type I collagen gels to be used as scaffolds for tissue engineering.

Investigations of high molecular weight recombinant protein triblock copolymers demonstrate unique opportunities to systematically modify material microstructure on both nano-and mesolength scales in a manner not been previously demonstrated for protein polymer systems. Significantly, through the biosynthesis of BAB-type copolymers containing flanking, plastic-like end blocks and an elastomeric midblock, virtually cross-linked protein-based materials were generated that exhibit tunable properties in a manner completely analogous to synthetic thermoplastic elastomers. Through the rational choice of processing conditions that control meso-and nanoscale structure, changes of greater than 3 orders of magnitude in Young's modulus (0.03-35 MPa) and 5-fold in elongation to break (250-1300%) were observed. Extensibility of this range or magnitude has not been previously reported for virtually cross-linked copolymers that have been produced by either chemical or biosynthetic approaches. We anticipate that these versatile protein-based thermoplastic elastomers will find applications as novel scaffolds for tissue engineering and as new biomaterials for controlled drug release and cell encapsulation.

GSF exhibits the fastest surface crystallization kinetics among the known amorphous pharmaceutical solids. Well below T (g), surface crystallization dominated the overall crystallization kinetics of amorphous GSF powder. Thus, surface crystallization should be distinguished from bulk crystallization in studying, modeling and controlling the crystallization of amorphous solids.

The well accepted "free drug hypothesis" for small-molecule drugs assumes that only the free (unbound) drug concentration at the therapeutic target can elicit a pharmacologic effect. Unbound (free) drug concentrations in plasma are readily measurable and are often used as surrogates for the drug concentrations at the site of pharmacologic action in pharmacokinetic-pharmacodynamic analysis and clinical dose projection in drug discovery. Furthermore, for permeable compounds at pharmacokinetic steady state, the free drug concentration in tissue is likely a close approximation of that in plasma; however, several factors can create and maintain disequilibrium between the free drug concentration in plasma and tissue, leading to free drug concentration asymmetry. These factors include drug uptake and extrusion mechanisms involving the uptake and efflux drug transporters, intracellular biotransformation of prodrugs, membrane receptor-mediated uptake of antibody-drug conjugates, pH gradients, unique distribution properties (covalent binders, nanoparticles), and local drug delivery (e.g., inhalation). The impact of these factors on the free drug concentrations in tissues can be represented by K p,uu , the ratio of free drug concentration between tissue and plasma at steady state. This review focuses on situations in which free drug concentrations in tissues may differ from those in plasma (e.g., K p,uu > or <1) and discusses the limitations of the surrogate approach of using plasmafree drug concentration to predict free drug concentrations in tissue. This is an important consideration for novel therapeutic modalities since systemic exposure as a driver of pharmacologic effects may provide limited value in guiding compound optimization, selection, and advancement. Ultimately, a deeper understanding of the relationship between free drug concentrations in plasma and tissues is needed.

The application of twin screw extrusion (TSE) as a scalable and green process for the manufacture of cocrystals was investigated. Four model cocrystal forming systems, Caffeine-Oxalic acid, Nicotinamide-trans cinnamic acid, Carbamazepine-Saccharin, and Theophylline-Citric acid, were selected for the study. The parameters of the extrusion process that influenced cocrystal formation were examined. TSE was found to be an effective method to make cocrystals for all four systems studied. It was demonstrated that temperature and extent of mixing in the extruder were the primary process parameters that influenced extent of conversion to the cocrystal in neat TSE experiments. In addition to neat extrusion, liquid-assisted TSE was also demonstrated for the first time as a viable process for making cocrystals. Notably, the use of catalytic amount of benign solvents led to a lowering of processing temperatures required to form the cocrystal in the extruder. TSE should be considered as an efficient, scalable, and environmentally friendly process for the manufacture of cocrystals with little to no solvent requirements.

The existence of a cocrystal between curcumin (CUR) and phloroglucinol (PHL) was suspected but could not be demonstrated in a recent systematic effort to synthesize novel curcumin cocrystals. We hypothesize that the elusive CUR–PHL cocrystal is a kinetically stable form that can be prepared by trapping it using a fast solvent removal crystallization process. The polarity of crystallization solvent and relative solubility of cocrystal formers in the solvent appear to be critical parameters governing the phase purity of the resulting cocrystal. Organic solvents of higher polarity and in which the cocrystal formers exhibited congruent solubility tended to afford a purer cocrystal phase. Essentially phase-pure CUR–PHL cocrystals were successfully obtained from acetone, and their 1:1 stoichiometry was confirmed by differential scanning calorimetry and solid state nuclear magnetic resonance spectroscopy. Compared with the individual component phases, the cocrystal displayed reduced hygroscopicity and improved tabletability. However, the intrinsic dissolution rate of the cocrystal showed no significant improvement compared with the pure CUR crystal due to the instantaneous conversion of the cocrystal to CUR at its surface upon contact with the dissolution medium.