Molecular dynamics simulation of interaction of the anti-cancer drug paclitaxel with the cell membrane: investigation of changes in van der Waals energy and center of mass

Due to increasing of cancers and production of new anti-cancer drugs for its treatment, in this study, the interaction of new hydrophobic anti-cancer drug paclitaxel with the cell membrane has been discussed using computational tools. We have done molecular dynamics simulation using NAMD and also the initial structures that were achieved from the protein data bank have been modified using VMD package. Langevin algorithm was used for temperature control in 310 K, the human body temperature and the Brandson algorithm was utilized for pressure control in 1 bar. The simulation has been done during 10 ns. The simulation equations were based on Newton’s Motion Law and a Lenard−Jones potential. The anti-cancer drug paclitaxel interaction with the cell membrane has been investigated from the van der Waals energy and center of mass (COM) perspectives that show less stability and low absorption of the drug to the cell membrane. Computational results of this study confirm the validity of previously published computational and laboratory studies. According to the drug hydrophobicity, less stability, low absorption and also low efficacy has been shown in interaction with the cell membrane. As a result, administration of the anti-cancer drug can be very effective and efficient by using new drug delivery methods

GelMA/TCP nanocomposite scaffold for vital pulp therapy

Pulp capping is a necessary procedure for preserving the vitality and health of the dental pulp, playing a crucial role in preventing the need for root canal treatment or tooth extraction. Here, we developed an electrospun gelatin methacryloyl (GelMA) fibrous scaffold incorporating beta-tricalcium phosphate (TCP) particles for pulp capping. A comprehensive morphological, physical-chemical, and mechanical characterization of the engineered fibrous scaffolds was performed. In vitro bioactivity, cell compatibility, and odontogenic differentiation potential of the scaffolds in dental pulp stem cells (DPSCs) were also evaluated. A pre-clinical in vivo model was used to determine the therapeutic role of the GelMA/TCP scaffolds in promoting hard tissue formation. Morphological, chemical, and thermal analyses confirmed effective TCP incorporation in the GelMA nanofibers. The GelMA+20%TCP nanofibrous scaffold exhibited bead-free morphology and suitable mechanical and degradation properties. In vitro, GelMA+20%TCP scaffolds supported apatite-like formation, improved cell spreading, and increased deposition of mineralization nodules. Gene expression analysis revealed upregulation of ALPL, RUNX2, COL1A1, and DMP1 in the presence of TCP-laden scaffolds. In vivo, analyses showed mild inflammatory reaction upon scaffolds' contact while supporting mineralized tissue formation. Although the levels of Nestin and DMP1 proteins did not exceed those associated with the clinical reference treatment (i.e., mineral trioxide aggregate), the GelMA+20%TCP scaffold exhibited comparable levels, thus suggesting the emergence of differentiated odontoblast-like cells capable of dentin matrix secretion. Our innovative GelMA/TCP scaffold represents a simplified and efficient alternative to conventional pulp-capping biomaterials. STATEMENT OF SIGNIFICANCE: Vital pulp therapy (VPT) aims to preserve dental pulp vitality and avoid root canal treatment. Biomaterials that bolster mineralized tissue regeneration with ease of use are still lacking. We successfully engineered gelatin methacryloyl (GelMA) electrospun scaffolds incorporated with beta-tricalcium phosphate (TCP) for VPT. Notably, electrospun GelMA-based scaffolds containing 20% (w/v) of TCP exhibited favorable mechanical properties and degradation, cytocompatibility, and mineralization potential indicated by apatite-like structures in vitro and mineralized tissue deposition in vivo, although not surpassing those associated with the standard of care. Collectively, our innovative GelMA/TCP scaffold represents a simplified alternative to conventional pulp capping materials such as MTA and Biodentine™ since it is a ready-to-use biomaterial, requires no setting time, and is therapeutically effective.</p