Tailoring electrospun nanofibers and electrosprayed nanoparticles to enhance cellular uptake of low bioavailability drugs

Noureen, Erum (2020) Tailoring electrospun nanofibers and electrosprayed nanoparticles to enhance cellular uptake of low bioavailability drugs. Doctoral thesis, London Metropolitan University.

Abstract

This thesis describes colon targeted, fast dissolving delivery systems prepared through electrospraying and electrospinning. An overview of relevant literature on electrospraying and electrospinning is given at the start. Biodegradable polymer polyvinylpyrrolidone (PVP), and polycaprolactone (PCL) were used in the projects to produce nanomaterials using simple and straight forward techniques of electrospinning and electrospraying.

In the first project, preparation, and characterization of PCL and PVP nanoparticles, using coaxial electrospraying was carried out. Electrosprayed nanocomposite coaxial nanoparticles with polyvinylpyrrolidone 10000 (PVP10) in the shell and polycaprolactone (PCL) 14000 in the core, were fabricated. Spherical, fiber-free particles were obtained with 5% solutions of polyvinylpyrrolidone. Confirmation of the presence of polycaprolactone inside the polyvinylpyrrolidone particles remained a challenge. Due to time constraints further work on this aspect of the project was abandoned, but a useful outcome was that low molecular weight PVP (av. mw10 kDa) could be used to prepare particles less than 100 nm.

For the second project, hemin was selected for preparation of formulations for treatment of anaemia, as current treatments have side effects like gastric irritation and low bioavailability. Electrospun nanofibers and electrosprayed nanoparticles were tailored to enhance cellular uptake of low bioavailability drugs (hemin). DMF and MeOH was used to make hemin soluble. PVP-360 and eudragit L 100 were initially selected to make hemin formulations by electrospinning. A variety of electrospinning conditions were attempted and optimal conditions for producing high quality fibers were found to be 0.5 mL/hr, 14 cm (distance) and 12.22 kV (voltage) for PVP/1% (w/w) hemin fibers. Preliminary dissolution tests showed that PVP/ hemin fibres completely dissolved in PBS within 10 minutes. Whereas eudragit/hemin fibres took 2 to 3 days to dissolve. PVP-360 made hemin dissolve successfully in PBS, so further development was focused on developing PVP formulations.

DLS (Dynamic light scattering) gave two or three sizes of populations in biological media. The proportion of aggregates increased as the concentration of hemin increased which might be due to hydrogen bond between PVP and hemin.

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