Abstract
The work demonstrates the preparation of PLGA (PLGA 50:50, PLGA 75:25) nanoparticles, to encapsulate a hydrophobic molecule (coumarin-6), using the microreactor-based continuous process. The formulations were characterized using dynamic light scattering and transmission electron microscopy to determine their size, homogeneity, zeta potential, and surface morphology. The resulting nanoparticles were safe to the CHO cells (≈80% cell survival), at the concentration of ≤600 µg/mL and were successfully taken up by the cells, as demonstrated using confocal microscopy. Moreover, imaging flow cytometry confirmed that the nanoparticles were internalized in 73.96% of the cells. Furthermore, molecular dynamics simulation and docking studies were carried out to explore the effect of polymer chain length of PLGA and lactide vs glycolide (LA:GA) ratio on their compatibility with the coumarin-6 molecules and to study the coiling and flexibility of PLGA in the presence of coumarin-6 molecules. Flory–Huggins interaction parameter (χ) was calculated for polymer chains of varying lengths and LA:GA ratio, with respect to coumarin-6. χ parameter increased with increase in polymer chain length, which indicated superior interaction of coumarin-6 with the smaller chains. Amongst all the polymeric systems, PLGA55 exhibited the strongest interaction with coumarin-6, for all the chain lengths, possibly because of their homogeneous spatial arrangements and superior binding energy. PLGA27 showed better compatibility compared to PLGA72 and PGA, whereas PLA-based polymers exhibited the least compatibility. Analysis of the radius of gyration of the polymer chains in the polymer–coumarin-6 complexes, at the end of molecular dynamics run, exhibited that the polymer chains displayed varying coiling behavior and flexibility, depending upon the relative concentrations of the polymer and coumarin-6. Factors like intra-chain interactions, spatial arrangement, inter-chain binding energies, and polymer–coumarin-6 compatibility also influenced the coiling and flexibility of polymer chains.
Highlights
Particulate systems of biodegradable polymers have been extensively explored for controlled and targeted delivery of various drugs and biomolecules [1, 2]
The results indicated that coumarin6-loaded PLGA NPs interacted with and adhered to the surface of CHO cells
The χ parameter of these polymer chains with coumarin-6 molecules was dependent on their mixing energy, which was in turn dependent on the binding energy of the
Summary
Particulate systems of biodegradable polymers have been extensively explored for controlled and targeted delivery of various drugs and biomolecules [1, 2]. Amongst the FDA-approved biocompatible polymers, lactide (LA) and glycolide (GA) based poly (lactic-co-glycolic acid) (PLGA)-based copolymers have enormous potential as demonstrated by their extensive use in drug/ protein/gene encapsulation [6,7,8], scaffold/stent preparation [9, 10], electronic, imaging devices [11, 12], etc. [14, 15] These methods employ high-speed homogenizers and are energy intensive. These processes cannot be adequately controlled and result in variable particle formation, due to rapidity of mixing, nucleation, and particle growth [16]. In the present investigation we have prepared the nanoparticles by continuous process that enables the generation of reproducible and uniformly distributed nanoemulsions
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