Globular chitosan treatment of bovine jugular veins: evidence of anticalcification efficacy in the subcutaneous rat model.

Vascular xenografts are widely used in cardiovascular surgery as an alternative to autologous vessels and vascular allografts. Calcification is one of the main drawbacks of vascular grafts, especially among young patients and children. Among different anticalcification approaches, chitosan emerges as a highly promising candidate due to its versatility, natural origin, and biocompatibility. We investigated the anticalcification efficacy of globular chitosan ("Chitozol") as it demonstrated the improved rate of water solubility as compared with conventional linear macromolecules of chitosan. In addition, we supposed that compact globular form of "Chitozol" molecules could provide effective penetration of extracellular matrix of bovine jugular veins (BJVs). Our results revealed that "Chitozol" treatment mitigated calcification in the experimental groups as compared to the control groups (without any treatment, conventional treatment with glutaraldehyde, and commercially available Contegra conduit). Different concentrations of "Chitozol" (0.3% and 3%), as well as different incubation times (15 and 30min), were equally effective in the prevention of calcification. In addition, "Chitozol" treatment with decellularization of BJVs demonstrated slightly improved stress-strain properties of unimplanted samples. Thus, the filling of fresh BJV with globular chitosan is proposed as a promising emerging treatment for the mitigation of calcific degeneration in BJVs xenografts.

A new method of producing monoclinic paracetamol suitable for direct compression.

PURPOSE: To develop a technique of obtaining monoclinic polymorph of paracetamol suitable for direct compression without excipients. METHODS: Preparation of spongy monoclinic paracetamol was based on quench-cooling of paracetamol solutions in water-acetone mixtures sprayed into a vessel with liquid nitrogen followed by removal of solvents by freeze-drying. X-ray powder diffraction was used to study annealing of quench-cooled solutions in "paracetamol-acetone-water" and "acetone-water" systems and to find optimum conditions for obtaining fine particles of pure monoclinic paracetamol. Samples were characterized by electron microscopy; compression properties were measured. RESULTS: The preparation technique gave fine monoclinic paracetamol powder containing agglomerates (30-200 µm) composed of flat particles (linear sizes 1-10 µm, the thickness 60-150 nm). The spongy sample was suitable for direct compression without excipients, stable on storage, and mechanically robust. Mechanically stable tablets pressed from the spongy sample were better soluble in water than commercially available tablets of paracetamol with excipients. CONCLUSIONS: The proposed method gave spongy monoclinic paracetamol samples with improved properties. For inexpensive paracetamol, the method may not yield economic advantage. However, the same method based on freeze-drying solutions in mixed aqueous-organic solvents can be used to prepare new improved forms of other molecular solids for pharmaceutical applications.

Calorimetric and X-ray studies of clathrate hydrates of tetraisoamylammonium polyacrylates.

The structure of clathrate hydrates with tetraisoamylammonium polyacrylate salt incorporated as guest has been studied in this work. Also, quantitative studies on the stability changes of the clathrate hydrates with different degrees of cross-linking of the guest polymer (varied from 0 to 3%) have been conducted. A single crystal X-ray diffraction study of a crystal of the hydrate with linear (uncross-linked) tetraisoamylammonium polyacrylate as guest reveals a hexagonal structure (space group P6m2, a = 12.15 A, c =12.58 A at 100 K) with 39 host framework water molecules per one guest monomeric unit. Powder X-ray diffraction analyses confirm the identity of the above crystal structure of the hydrate with linear guest polymer and the crystal structure of the hydrates with cross-linked guest (hexagonal, a = 12.25 A, c =12.72 A at 276 K). In order to quantitatively determine the stability differences of the hydrates with the included guests having various degrees of cross-linking of the anionic chain, a series of differential scanning calorimetry measurements of the fusion enthalpy of the hydrate samples has been carried out. On the basis of the results obtained, a structural model describing the decrease in the stability of the clathrate hydrates with tetraisoamylammonium polyacrylate guest as a function of the degree of cross-linking of the guest polymer has been suggested.