Polymer−Drug Interactions in Tyrosine-Derived Triblock Copolymer Nanospheres: A Computational Modeling Approach

Abstract

A combination of Molecular Dynamics (MD) simulations and docking calculations was employed to model and predict polymer-drug interactions in self-assembled nanoparticles consisting of ABA-type triblock copolymers, where A-blocks are poly(ethylene glycol) units and B-blocks are low molecular weight tyrosine-derived polyarylates. This new computational approach was tested on three representative model compounds: nutraceutical curcumin, anti-cancer drug paclitaxel and pre-hormone vitamin D3. Based on this methodology, the calculated binding energies of polymer-drug complexes can be correlated with maximum drug loading determined experimentally. Furthermore, the modeling results provide an enhanced understanding of polymer-drug interactions, revealing subtle structural features that can significantly affect the effectiveness of drug loading (as demonstrated for a fourth tested compound, anticancer drug camptothecin). The present study suggests that computational calculations of polymer-drug pairs hold the potential of becoming a powerful prescreening tool in the process of discovery, development and optimization of new drug delivery systems, reducing both the time and the cost of the process.

A Review on Cuminosides Nanomedicine-: Pharmacognostic approach to Cancer therapeutics

“…Recent investigations also rely on transmission electron microscopy to further validate cuminosides nanoformulations cellular uptake (internalization). 41,51 These investigations provide clear evidence of the presence of nanoparticle internalization at higher magnification. Another convenient method established for the determination of cellular uptake is Prussian blue staining.…”

“…Similarly, some of these formulations show decreased uptake in macrophage or normal cells which suggests the reticuloendothelial system (RES) clearance of nanoparticles is avoided. 51 Such a selective and improved intracellular accumulation or uptake of cuminosides nanoformulations in cancer cells is an indication for a higher therapeutic index. The extent of cellular uptake of cuminosides depends on the type of nanocarrier, particle size, surface charge, and cell line.…”

“…Numerous reports of various drug nanoformulations support this phenomenon. Researchers 51 have demonstrated that a chitogen based nanocarrier enhances the internalization in MCF-7 and PC-3 cancer cells as time increased from 1 h to 48 h. The cuminosides levels are increased from 0.2 to 0.8% absorbance in UV-vis spectral study. We also learn that the uptake by various cancer cells is quite different and vary formulation to formulation.…”

“…However, the targeting specificity of cuminosides nanoformulations towards cancer cells can be improved via antibody, peptide, penetrating ligand or aptamer conjugation. 15 After exposure of cuminosides nanoformulations to cancer cells, many nanoparticles were localized in the cytoplasm and inside or around the nucleus, 41,51 longer periods of exposure drastically changed the morphology (e.g., cell lysis and loss of spindle shape) of cancer cells and observed cell debris. This type of behavior is highly dependent upon typical physico- chemical properties such as amorphous, crystalline, particle size and morphology and surface charge of the nanoformulations.…”

“…This phenomenon most likely occurred due to the transport of drug to the nucleus of the cell which induced the activity of the telomerase. A core-shell cuminosides-loaded nanoparticle generated by amphilic methoxy polyethylene glycol-poly (caprolactone) (mPEG-PCL) block copolymers has shown similar effects in a rat C6 glioma cell line 51 Cuminosides encapsulation in a chitosan (CS) and silk fibroin (SF) blend polymer showed significantly lower IC 50 than SF-encapsulated cuminosides Her2/ neu (low and high) expressing breast cancer cells. 44 Numerous cuminosides nanoformulations have exhibited very similar anticancer potential compared to free cuminosides.…”