Harnessing Polyhydroxyalkanoates and Pressurized Gyration for Hard and Soft Tissue Engineering.

Organ dysfunction is a major cause of morbidity and mortality. Transplantation is typically the only definitive cure, challenged by the lack of sufficient donor organs. Tissue engineering encompasses the development of biomaterial scaffolds to support cell attachment, proliferation, and differentiation, leading to tissue regeneration. For efficient clinical translation, the forming technology utilized must be suitable for mass production. Herein, uniaxial polyhydroxyalkanoate scaffolds manufactured by pressurized gyration, a hybrid scalable spinning technique, are successfully used in bone, nerve, and cardiovascular applications. Chorioallantoic membrane and in vivo studies provided evidence of vascularization, collagen deposition, and cellular invasion for bone tissue engineering. Highly efficient axonal outgrowth was observed in dorsal root ganglion-based 3D ex vivo models. Human induced pluripotent stem cell derived cardiomyocytes exhibited a mature cardiomyocyte phenotype with optimal calcium handling. This study confirms that engineered polyhydroxyalkanoate-based gyrospun fibers provide an exciting and unique toolbox for the development of scalable scaffolds for both hard and soft tissue regeneration.

Copolymer Composition and Nanoparticle Configuration Enhance in vitro Drug Release Behavior of Poorly Water-soluble Progesterone for Oral Formulations.

HYPOTHESIS: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone. EXPERIMENTS: Six formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior. FINDINGS: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1±54.8 to 588.0±92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9±1.4% and 70.7±3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0±1.7% and 57.5±2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro.

Characterisation of the Chemical Composition and Structural Features of Novel Antimicrobial Nanoparticles.

Three antimicrobial nanoparticle types (AMNP0, AMNP1, and AMNP2) produced using the TesimaTM thermal plasma technology were investigated and their compositions were determined using a combination of analytical methods. Scanning electron micrographs provided the morphology of these particles with observed sizes ranging from 10 to 50 nm, whilst FTIR spectra confirmed the absence of polar bonds and organic impurities, and strong Raman active vibrational bands at ca. 1604 and 1311 cm-1 ascribed to C-C vibrational motions were observed. Carbon signals that resonated at δC 126 ppm in the solid state NMR spectra confirmed that sp² hybridised carbons were present in high concentration in two of the nanoparticle types (AMNP1 and AMNP2). X-ray powder diffraction suggested that AMNP0 contains single phase Tungsten carbide (WC) in a high state of purity and multiple phases of WC/WC1-x were identified in both AMNP1 and AMNP2. Finally, X-ray photoelectron spectral (XPS) analyses revealed and quantified the elemental ratios in these composite formulations.

Mebeverine-loaded electrospun nanofibers: physicochemical characterization and dissolution studies.

Both fast dissolving and sustained release drug delivery systems (DDSs) comprising mebeverine hydrochloride (MB-HCl) embedded in either povidone (PVP) K60 or Eudragit(®) L 100-55 nanofibers have been prepared by electrospinning. The fibers are found to have cylindrical morphologies with smooth surfaces, except at high drug loadings that appear to induce surface roughness (PVP) or fragmentation (Eudragit). There is a general increase in fiber diameter with drug loading. Differential scanning calorimetry and X-ray diffraction demonstrate that the drug exists in an amorphous state in the fibers. Infrared spectroscopy data indicate that the drug has good compatibility with the polymer, whereas nuclear magnetic resonance spectroscopy and high-performance liquid chromatography analyses confirmed that the MB-HCl was not degraded during the spinning process. In vitro dissolution tests of the PVP fiber mats show them to dissolve within 10 s, an improved dissolution profile over the pure drug. The Eudragit fibers show pH-dependent drug release profiles, with only very limited release at pH 2.0 but sustained release over approximately 8 h at pH 6.8. The Eudragit nanofibers have the potential to be developed as oral DDSs for localized drug release in the intestinal tract, whereas the PVP materials may find the application as buccal delivery systems or suppositories.