Conjugation of polybasic dendrimers with neutral grafts: effect on conformation and encapsulation of acidic drugs

Abstract

We examine the role of neutral dendrimer grafts upon the conformations and the drug complexation efficacy of weakly basic polyelectrolyte dendrimers by using a self-consistent field theory approach. Our results indicate that grafted chains modify the conformations of the dendrimers and lead to a swelling of the dendrimer, the degree of which increases with increasing chain length of the grafts. In turn, such conformational changes leads to a higher charge being carried by the dendrimer molecule. We compare the encapsulation efficacy of grafted and non-grafted dendrimers and find that for strong enough enthalpic and/or electrostatic interactions, the grafted dendrimers are capable of higher amounts of encapsulation than the non-grafted counterparts. By isolating the influences of electrostatic and enthalpic interactions, we clarify the physics behind the observed enhanced encapsulation.

Fe3O4@mSiO2 core–shell nanocomposite capped with disulfide gatekeepers for enzyme-sensitive controlled release of anti-cancer drugs

“…The controlled-release process can be regulated either by external stimuli such as thermal, light, electrostatic, magnetic actuation, and photoirradiation, or by internal stimuli such as pH and enzymes. [16][17][18][19][20] For instance, Yang and co-workers constructed a novel cancer theranostic hybrid platform, based on mesoporous silica-coated gold nanorods gated by sulfonatocalix [4]arene switches, for biofriendly near-infrared (NIR) light-triggered cargo release in a remote and stepwise fashion. 21 Zhu et al successfully demonstrated a pH-triggered controlled drug release system by the dissolution of ZnO nanolids in acidic conditions, showing a valuable pH-responsive strategy for the delivery of anticancer agents.…”

A New Self-Consistent Field Model of Polymer/Nanoparticle Mixture

“…It is also able to reveal the entropic and enthalpic contributions in the variation of morphologies. Overall, it is a valuable approach to explore and analyze the rich mesostructures or particle-induced defects 49 in polymer-based nanocomposites and is also readily extendable to the study of biology-related systems, such as dendrimer/drug encapsulation 50 and membrane/particle assembly 51 .…”

Pharmacoinformatic approaches to understand complexation of dendrimeric nanoparticles with drugs

“…To gain an insight into the mechanism behind the solubilization of weakly acidic drugs via dendrimeric nanoparticles, Lewis and Ganesan 125,126 developed self-consistent eld theory model for charged dendrimers and studied the individual as well as synergistic effects of excluded volume interactions, electrostatic attractions, and enthalpic interactions (hydrophobic and hydrogen bonding) on the solubilisation of weakly acidic drug molecules. The relative importance of different parameters like generation number, solution pOH and Bjerrum length, drug size, concentration and hydrophobicity, and strength of drugpolymer interactions were explored in terms of encapsulation efficiency of dendrimer.…”