KEYWORDS: Imaging spectroscopy, Microfluidics, Diagnostics, In vitro testing, Fluorescence spectroscopy, Spectroscopes, Luminescence, Optical fibers, Animal model studies, Tissues, Bone, Lab on a chip, In vivo imaging
Microfluidic device based diagnostics involving optical fibre path, in situ imaging and spectroscopy are
gaining importance due to recent advances in diagnostics instrumentation and methods, besides other
factors such as low amount of reagent required for analysis, short investigation times, and potential
possibilities to replace animal model based study in near future. It is possible to grow and monitor tissues in
vitro in microfluidic lab-on-chip. It may become a transformative way of studying how cells interact with
drugs, pathogens and biomaterials in physiologically relevant microenvironments. To a large extent,
progress in developing clinically viable solutions has been constrained because of (i) contradiction between
in vitro and in vivo results and (ii) animal model based and clinical studies which is very expensive. Our
study here aims to evaluate the usefulness of microfluidic device based 3D tissue growth and monitoring
approach to better emulate physiologically and clinically relevant microenvironments in comparison to
conventional in vitro 2D culture. Moreover, the microfluidic methodology permits precise high-throughput
investigations through real-time imaging while using very small amounts of reagents and cells. In the
present study, we report on the details of an osteoblast cell based 3D microfluidic platform which we
employ for osteogenic drug screening. The drug formulation is functionalized with fluorescence and other
biomarkers for imaging and spectroscopy, respectively. Optical fibre coupled paths are used to obtain
insight regarding the role of stress/flow pressure fluctuation and nanoparticle-drug concentration on the
osteoblast growth and osteogenic properties of bone.
By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.
pH-sensitive photonic composite hydrogel beads composed of sodium alginate and risedronate sodium (SA/RIS) was
prepared crosslinked by Ca2+ owing to the ionic gelation of SA. The structure and surface morphology of the composite hydrogel beads were characterized by SEM. pH-sensitivity of these composite hydrogels beads and the
release behaviors of drug from them were investigated. The results showed that the composite hydrogel beads had
good pH-sensitivity. The drug loading and encapsulation efficiency were 27.7% and 92% for RIS, respectively. The
cumulative release ratios of RIS from the composite hydrogel beads were 2.47% in pH 2.1 solution and 83 % in pH 6.8 solutions within 24 h, respectively. However, the cumulative release ratio of RIS in pH 7.4 solution reached 91% within 7 h. It is proposed that the novel photonic SA/RIS composite hydrogel bead could possess the potential of an increased intestinal absorption and fewer adverse effects of RIS. The pH and salt response of photonic hydrogel bead,
as well as the encapsulation of macromolecules, are promising for applications in biomedicine and biotechnology.
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