Selective Targeting of Lung Cancer Cells with Methylparaben-Tethered-Quinidine Cocrystals in 3D Spheroid Models.

The development and design of pharmaceutical cocrystals for various biological applications has garnered significant interest. In this study, we have established methodologies for the growth of the methylparaben-quinidine cocrystal (MP-QU), which exhibits a well-defined order that favors structure-property correlation. To confirm the cocrystal formation, we subjected the cocrystals to various physicochemical analyses such as powder X-ray diffraction (PXRD), single-crystal X-ray diffraction (SCXRD), Raman, and IR spectroscopy. The results of the XRD pattern comparisons indicated no polymorphisms, and density functional theory (DFT) studies in both gaseous and liquid phases revealed enhanced stability. Our in silico docking studies demonstrated the cocrystal's high-affinity binding towards cancer-specific epidermal growth factor receptor (EGFR), Janus kinase (JAK), and other receptors. Furthermore, in vitro testing against three-dimensional (3D) spheroids of lung cancer (A549) and normal fibroblast cells (L929) demonstrated the cocrystal's higher anticancer potential, supported by cell viability measurements and live/dead assays. Interestingly, the cocrystal showed selectivity between cancerous and normal 3D spheroids. We found that the MP-QU cocrystal inhibited migration and invadopodia formation of cancer spheroids in a favorable 3D microenvironment.

Biocompatibility-on-a-chip: Characterization and evaluation of decellularized tendon extracellular matrix (tdECM) hydrogel for 3D stem cell culture in a microfluidic device.

Researchers have always tried expensive in vitro tests to show the 3D usability of dECM. The use of tissue-specific hydrogels in a microfluidic device is rarely studied. In this study, we have used ECM obtained from goat digital flexor tendons by decellularization technique. The tdECM was characterized for its structural properties using Scanning Electron Microscopy (SEM). Collagen, dsDNA, GAGs, and protein contents were quantified using spectrophotometric assays. The cell viability and proliferation of human umbilical cord-derived mesenchymal stem cells (hUMSCs) encapsulated in the tdECM hydrogel inside the microfluidic device were checked using Calcein-AM/PI. The FTIR data showed prominent peaks of the amide group, indicating the presence of collagen. The SEM data showed intact fiber morphology after the decellularization process. There was a 95 % reduction in double-stranded DNA (dsDNA) content, proving the effectiveness of the decellularization technique. There was no significant difference in the collagen content of tdECM and the GAGs were also in the acceptable range compared to the native tissue. Over 90 % cell viability in hUMSCs was observed qualitatively and quantitatively in vitro and inside a microfluidic device. In conclusion, we characterized the tdECM hydrogel and demonstrated its compatibility with the microfluidic device.

Electrospun freestanding hydrophobic fabric as a potential polymer semi-permeable membrane for islet encapsulation.

One of the significant problems associated with islet encapsulation for type 1 diabetes treatment is the loss of islet functionality or cell death after transplantation because of the unfavorable environment for the cells. In this work, we propose a simple strategy to fabricate electrospun membranes that will provide a favorable environment for proper islet function and also a desirable pore size to cease cellular infiltration, protecting the encapsulated islet from immune cells. By electrospinning the wettability of three different biocompatible polymers: cellulose acetate (CA), polyethersulfone (PES), and polytetrafluoroethylene (PTFE) was greatly modified. The contact angle of electrospun CA, PES, and PTFE increased to 136°, 126°, and 155° as compared to 55°, 71°, and 128° respectively as a thin film, making the electrospun membranes hydrophobic. Commercial porous membranes of PES and PTFE show a contact angle of 30° and 118°, respectively, confirming the hydrophobicity of electrospun membranes is due to the surface morphology induced by electrospinning. In- vivo results confirm that the induced hydrophobicity and surface morphology of electrospun membranes impede cell attachment, which would help in maintaining the 3D circular morphology of islet cell. More importantly, the pore size of 0.3-0.6 µm obtained due to the densely packed structure of nanofibers, will be able to restrict immune cells but would allow free movement of molecules like insulin and glucose. Therefore, electrospun polymer fibrous membranes as fabricated in this work, with hydrophobic and porous properties, make a strong case for successful islet encapsulation.