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

Abstract

Drug delivery platforms are anticipated to have biocompatible and bioinert surfaces. PEGylation of drug carriers is the most approved method since it improves water solubility and colloid stability and decreases the drug vehicles’ interactions with blood components. Although this approach extends their biocompatibility, biorecognition mechanisms prevent them from biodistribution and thus efficient drug transfer. Recent studies have shown (poly)­zwitterions to be alternatives for PEG with superior biocompatibility. (Poly)­zwitterions are super hydrophilic, mainly stimuli-responsive, easy to functionalize and they display an extremely low protein adsorption and long biodistribution time. These unique characteristics make them already promising candidates as drug delivery carriers. Furthermore, since they have highly dense charged groups with opposite signs, (poly)­zwitterions are intensely hydrated under physiological conditions. This exceptional hydration potential makes them ideal for the design of therapeutic vehicles with antifouling capability, i.e., preventing undesired sorption of biologics from the human body in the drug delivery vehicle. Therefore, (poly)­zwitterionic materials have been broadly applied in stimuli-responsive “intelligent” drug delivery systems as well as tumor-targeting carriers because of their excellent biocompatibility, low cytotoxicity, insignificant immunogenicity, high stability, and long circulation time. To tailor (poly)­zwitterionic drug vehicles, an interpretation of the structural and stimuli-responsive behavior of this type of polymer is essential. To this end, a direct study of molecular-level interactions, orientations, configurations, and physicochemical properties of (poly)­zwitterions is required, which can be achieved via molecular modeling, which has become an influential tool for discovering new materials and understanding diverse material phenomena. As the essential bridge between science and engineering, molecular simulations enable the fundamental understanding of the encapsulation and release behavior of intelligent drug-loaded (poly)­zwitterion nanoparticles and can help us to systematically design their next generations. When combined with experiments, modeling can make quantitative predictions. This perspective article aims to illustrate key recent developments in (poly)­zwitterion-based drug delivery systems. We summarize how to use predictive multiscale molecular modeling techniques to successfully boost the development of intelligent multifunctional (poly)­zwitterions-based systems.

Exploring Steroidal Surfactants as Potential Drug Carriers for an Anticancer Drug Curcumin: An Insight into the Effect of Surfactants’ Structure on the Photophysical Properties, Stability, and Activity of Curcumin

“…Moreover, zwitterionic-based drug carriers are known to exhibit superior biocompatibility, anti(bio)fouling property, negligible immunogenicity, higher cellular uptake of chemicals and drugs, etc. 44,45 Recently, the increasing attention toward the applications of zwitterionic moieties as drug carriers and therapeutics 45,46 offers immense opportunity to exploit this bioinspired surfactant in the field of drug delivery; also, a comparison with its bile salt analogues is considered necessary for the fundamental understanding and applications.…”

“…Moreover, zwitterionic-based drug carriers are known to exhibit superior biocompatibility, anti(bio)fouling property, negligible immunogenicity, higher cellular uptake of chemicals and drugs, etc. 44,45 Recently, the increasing attention toward the applications of zwitterionic moieties as drug carriers and therapeutics 45,46 offers immense opportunity to exploit this bioinspired surfactant in the field of drug delivery; also, a comparison with its bile salt analogues is considered necessary for the fundamental understanding and applications. Therefore, this work aims at a detailed and comparative analysis between CHAPS and six bile salt variants, namely, NaDC, NaC, sodium taurodeoxycholate (NaTDC), NaTC, sodium glycodeoxycholate (NaGDC), and sodium glycocholate (NaGC) (Scheme 1B), as possible vehicles for the anticancer drug curcumin to enhance its solubility, stability, and bioavailability.…”

Enhancing the Antitumor Efficacy of Zwitterionic Peptide-Based Nanoscale Micelles through Sensitizing Their Response in Solid Tumors

“…Thus, zwitterionic polymer-protected nanodrugs effectively escape phagocytosis of the endothelial reticular system to prolong their circulation time in vivo. , Recently, zwitterionic polypeptides were developed as more ideal nanocarrier materials since they can be enzymatically degraded for quickly releasing the loaded drug and are naturally metabolized after internalization. The nanodrugs, which are encapsulated by them, showed the characteristics of albumin, a major zwitterionic biomacromolecule covered by abundant glutamic acid (E) and lysine (K) with a negative charge bias in blood .…”

Calix[4]Resorcinarene Carboxybetaines and Carboxybetaine Esters: Synthesis, Investigation of In Vitro Toxicity, Anti-Platelet Effects, Anticoagulant Activity, and BSA Binding Affinities

“…When a nanosystem enters the blood, protein is adsorbed on the surface of the particle in seconds [ 33 ], but it can be prevented by “invisible” “stealth” mechanisms. Potential ways to limit the effects of plasma protein targeting include the use of pegylation and zwitterionic functionalization of the particle surface, which can limit protein adsorption and thus increase in vivo circulation time and prevent non-specific interactions with the immune system [ 34 , 35 ]. Nevertheless, the functionalization of amphiphilic calix[4]resorcinarenes with the potential for hydrophobic interactions with protein molecules by zwitterionic groups raises questions about the prediction of possible complex formation with plasma proteins.…”