Molecular insight into silk fibroin based delivery vehicle for amphiphilic drugs: Synthesis, characterization and molecular dynamics studies

• Published in: Journal of molecular liquids Vol. 299; p. 112156
• Main Authors: Montalbán, Mercedes G., Chakraborty, Sandipan, Peña-García, Jorge, Verli, Hugo, Villora, Gloria, Pérez-Sánchez, Horacio, Díaz-Baños, F. Guillermo
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2020
• Subjects: Blind docking; Drug loading; Encapsulation; Molecular dynamics; Encapsulation; Blind docking; Molecular dynamics; Drug loading
• ISSN: 0167-7322; 1873-3166
• DOI: 10.1016/j.molliq.2019.112156

Recent emergence of natural biopolymers as drug delivery vehicles is attributed to their biodegradability and less systemic toxicity. Here, we have synthesized curcumin, indomethacin and emodin-loaded silk fibroin nanoparticles (SFNs) and characterized several pharmacokinetic parameters (Drug Loading and Entrapment Efficiency). Silk fibroin is a highly promising bio-material with impressive mechanical properties, high bio-compatibility and it does not exert any immunological responses in vivo. Our results show that emodin almost released completely within 144 h, however a steady release profile has been observed for indomethacin which is attributed to its moderate loading and Entrapment Efficiency by SFNs. On the other hand, complete release of curcumin is not observed even in 168 h. Curcumin also shows very promising Drug Loading and Entrapment Efficiency when loaded within the SFNs matrix. Molecular level characterization with the aid of blind docking and molecular dynamics simulation reveals that the Entrapment efficiency of the drugs exactly follows the interaction energy patterns obtained from MM/PBSA calculation, i.e., curcumin > indomethacin > emodin. Strong binding energy of curcumin with the fibroin protein is attributed to the formation of more number of hydrogen bonds compared to the other two drugs and involvement in additional π-π stacking interactions. Indomethacin interacts moderately with the SFN primarily mediated through several van der Waals interactions which accounts for its sustained release from the SFN matrix. Emodin interacts with the fibroin protein very weakly which is responsible for its low encapsulation and observed diffusion controlled release behavior within the fibroin matrix. [Display omitted] •Amphiphilic drugs-loaded silk fibroin nanoparticles have been synthesized and characterized.•Encapsulation efficiency of the drugs exactly follows the interaction energy patterns.•Curcumin interacts with protein matrix through hydrogen bonds and π-π stacking interactions.•Indomethacin interacts moderately with the SFN mediated by van der Waals interactions.•Emodin interacts with the fibroin protein very weakly leads to diffusion controlled release.