Influence of lactide vs glycolide composition of poly (lactic-co-glycolic acid) polymers on encapsulation of hydrophobic molecules: molecular dynamics and formulation studies

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.

Modular Drug-Loaded Nanocapsules with Metal Dome Layers as a Platform for Obtaining Synergistic Therapeutic Biological Activities

“…To compare the drug release profiles and kinetics of the PLGA nanocapsules with and without metal deposition, release studies were performed by detecting the druglike fluorophore molecule coumarin-6. Interestingly, no significant differences were observed in the release profile and kinetics between the metal-coated and uncoated nanocapsules (∼41% over 168 h), being similar to other reports on the release kinetics of coumarin-6 from PLGA NPs (33–45% over 168 h). − A similar release pattern of the paclitaxel drug was also observed in our previous work for Fe-coated and uncoated polymer nanoparticles . These results indicate that neither the metal layer nor the deposition process reduced the percentage and extension of the drug release (Figure E), thereby preserving the water hydrolysis of the polymer chains that triggers the polymer degradation .…”

Native PLGA nanoparticles attenuate Aβ-seed induced tau aggregation under in vitro conditions: potential implication in Alzheimer’s disease pathology

“…Evidence suggests that interaction of PLGA polymers with biologically active molecules depends on their surface properties. PLGA 50:50, with its balanced ratio of lactic to glycolic acids presents a more hydrophilic surface 54 , 55 than the more hydrophobic PLGA 75:25 resomer. Tau protein, being predominantly hydrophilic and enriched with charged amino acids, it is likely to interact favorably with hydrophilic surfaces of PLGA 50:50 which could sterically hinder self-association of tau molecules leading to reduction in its aggregation.…”

Microreactor-based micro/nanomaterials: fabrication, advances, and outlook

“…They also found that the growth of individual Ag or Au nanodots can be controlled by varying the beam intensity, the concentration of the metal salt, and the flow rate within the microreactor. Dobhal et al 239 from the Institute of Chemical Technology in India prepared poly (lactic-co-glycolic acid) (PLGA)encapsulated coumarin-6 nanoparticles on a microreactor continuous platform. Multiple test results show that the nanoparticles are safe to CHO cells (E80% cell viability) at a concentration of r600 mg mL À1 and can be successfully absorbed by cells.…”

“…Dobhal et al 239 from the Institute of Chemical Technology in India prepared poly (lactic- co -glycolic acid) (PLGA)-encapsulated coumarin-6 nanoparticles on a microreactor continuous platform. Multiple test results show that the nanoparticles are safe to CHO cells (≈80% cell viability) at a concentration of ≤600 μg mL −1 and can be successfully absorbed by cells.…”