Molecular Modelling Guided Modulation of Molecular Shape and Charge for Design of Smart Self-Assembled Polymeric Drug Transporters

Abstract

Nanomedicine employs molecular materials for prevention and treatment of disease. Recently, smart nanoparticle (NP)-based drug delivery systems were developed for the advanced transport of drug molecules. Rationally engineered organic and inorganic NP platforms hold the promise of improving drug targeting, solubility, prolonged circulation, and tissue penetration. However, despite great progress in the synthesis of NP building blocks, more interdisciplinary research is needed to understand their self-assembly and optimize their performance as smart nanocarriers. Multi-scale modeling and simulations provide a valuable ally to experiment by mapping the potential energy landscape of self-assembly, translocation, and delivery of smart drug-loaded NPs. Here, we highlight key recent advances to illustrate the concepts, methods, and applications of smart polymer-based NP drug delivery. We summarize the key design principles emerging for advanced multifunctional polymer topologies, illustrating how the unusual architecture and chemistry of dendritic polymers, self-assembling polyelectrolytes and cyclic polymers can provide exceptional drug delivery platforms. We provide a roadmap outlining the opportunities and challenges for the effective use of predictive multiscale molecular modeling techniques to accelerate the development of smart polymer-based drug delivery systems.

Modeling Polyzwitterion-Based Drug Delivery Platforms: A Perspective of the Current State-of-the-Art and Beyond

“…It is needless to say how helpful having a deep understanding of the affinity contributions of attractive and repulsive interactions and the entropy contribution can be to engineer and tune supramolecular-based therapeutic vehicles. As one of the most effective tools, the multiscale modeling approach holds great promise in predicting the structure and response behavior of materials in various disciplines, including the design of drug carriers. , Visualization of experimental data in a three-dimensional atomic-scale model can assist in explaining phenomena and often raises new questions, thereby improving future research. − However, to study and design effective drug delivery systems using molecular modeling, a broad range of length and time scales needs to be spanned. In this regard, understanding the capabilities of different molecular modeling techniques such as ab initio quantum mechanics (QM), molecular dynamics (MD), Monte Carlo (MC) methods, and mesoscale (MS) methods in the drug delivery systems studies can assist us to select and well-parametrize proper modeling tools (more details of the simulation methods are presented in Table ).…”

“…In this regard, understanding the capabilities of different molecular modeling techniques such as ab initio quantum mechanics (QM), molecular dynamics (MD), Monte Carlo (MC) methods, and mesoscale (MS) methods in the drug delivery systems studies can assist us to select and well-parametrize proper modeling tools (more details of the simulation methods are presented in Table ). ,− From all these methods, QM techniques can explain any molecular systems behaviors at the atomistic level by computing the electron distribution but are limited in the system size they can tackle . All noncovalent interactions of various systems at atomic resolution can be monitored using MD simulations. , However, many critical problems in the drug delivery field happen at larger time and length scales far beyond what can be tackled using atomistic MD (force field).…”

Copolyelectrolyte-Based Nanocapsules for Oral Monoclonal Antibody Therapy: A Mesoscale Modeling Survey

“…We use a dissipative particle dynamics (DPD) coarse-grained molecular model commonly applied in studies of self-assemblies, membranes, and complex fluids. − A detailed discussion of the DPD model equations and parameters can be found elsewhere. , In a coarse-grained molecular model approach, such as DPD, beads represent groups of molecules or atoms, mapping the geometry and momentum of a section of fluid. , In DPD simulations, the particles interact through a soft repulsion potential, which allows the nonbonded particles to overlap. Therefore, two particles of opposite point charge may form an artificial ion-pair.…”

Polymeric Nanostructures Containing Proteins and Peptides for Pharmaceutical Applications

“…Stimuli-responsive polymers, so-called smart polymers, are the key factor in the latest generation of supramolecular nanocarriers, which are formed through the combination of the two categories. These polymers are able to undergo physicochemical changes or rearrangements due to their response to a specific stimulus, whether that be endogenous, such as to pH and redox variations, hypoxia, and enzymes, or exogenous, such as temperature alterations, light exposure, magnetic fields, and ultrasound, thereby enabling controlled release of active pharmaceutical ingredients (API) at specific sites [32,34,35].…”