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

Autor: Prajakta Dandekar, Ashu Srivastav, Anurag Dobhal, Ratnesh Jain
Rok vydání: 2021
Předmět:
Materials science
Drug Compounding
Polyesters
Biomedical Engineering
Biophysics
Bioengineering
CHO Cells
Molecular Dynamics Simulation
Flory–Huggins solution theory
Biomaterials
chemistry.chemical_compound
Molecular dynamics
Cricetulus
Microscopy
Electron
Transmission
Polylactic Acid-Polyglycolic Acid Copolymer
Dynamic light scattering
Coumarins
Materials Testing
Toxicity Tests
Medical technology
Zeta potential
Animals
heterocyclic compounds
Lactic Acid
Particle Size
R855-855.5
Materials of engineering and construction. Mechanics of materials
chemistry.chemical_classification
Drug Carriers
Lactide
Polymer
Biomaterials Synthesis and Characterization
Glycolates
PLGA
chemistry
Chemical engineering
TA401-492
Radius of gyration
Nanoparticles
Hydrophobic and Hydrophilic Interactions
Polyglycolic Acid
Zdroj: Journal of Materials Science: Materials in Medicine, Vol 32, Iss 10, Pp 1-18 (2021)
Journal of Materials Science. Materials in Medicine
ISSN: 1573-4838
0957-4530
Popis: 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 Microreactor-based continuous process for the synthesis of PLGA nanoparticles.Miscibility of different PLGA polymers and coumarin-6 was evaluated computationally.Flory–Huggins interaction parameter (χ) was superior for shorter PLGA chains, irrespective of their lactide to glycolide ratio.Polymer chains containing lactide to glycolide ratio of 1:1 resulted in strongest interaction with coumarin-6 due to homogeneous spatial arrangements and superior binding energy.Intra-chain interactions, spatial arrangement, inter-chain binding energies, and polymer–coumarin-6 miscibility influence coiling and flexibility of polymer chains.
Databáze: OpenAIRE
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