Drug Release from pH-Sensitive Polymeric Micelles with Different Drug Distributions: Insight from Coarse-Grained Simulations

Nie, Shu; Lin, Wen Jing; Yao, Na; Guo, Xin Dong; Zhang, Li Juan

doi:10.1021/am503920m

Cited by 67 publications

(47 citation statements)

References 53 publications

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“…17 The amphiphilic polymer hybrid NP consisting of three distinct functional components of hydrophobic polymeric core, hydrophilic polymeric shell and lipid monolayer, behaves as a robust drug delivery platform with high drug encapsulation yield, tunable and sustained drug release profile. [18][19][20][21] However, the design principles of synthetic nano-scaffolds with amphiphilic polymers for membrane transport are far from being comprehensively understood. The shell formed by the polymer can protect the core by decreasing the contact with inactivating species in the aqueous phase.…”

Section: Introductionmentioning

confidence: 99%

Designing Nanoparticle Translocation through Cell Membranes by Varying Amphiphilic Polymer Coatings

2015

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Nanoparticle-assisted drug delivery has been emerging as an active research area. Understanding and controlling the interaction of the coated-nanoparticles (NPs) with cell membranes is key to the development of the efficient drug delivery technologies and to the management of nanoparticle-related health and safety issues. Cellular uptake of nanoparticles coated with mixed hydrophilic/hydrophobic polymer ligands is known to be strongly influenced by the polymer pattern on the NP surface and remains open for further exploration. To unravel the physical mechanism behind this intriguing phenomenon, here we perform dissipative particle dynamics simulations to analyze the forces and efficacy time as the copolymer-coated NPs pass through the lipid bilayer so as to provide better design of coated-NPs for future drug delivery applications. Four characteristic copolymer ligands are constructed to perform the simulations: hydrophilic-hydrophobic (AB), hydrophobic-hydrophilic (BA), and hydrophobic-hydrophilichydrophobic-hydrophilic (BABA), and a random pattern with hydrophilic and hydrophobic beads. We mainly study the critical force and potential of mean force required for entering inside the lipid bilayer and penetration force to pass all the way through the cell membrane as well as the translocation time for these patterned NPs across the bilayer. Through copolymer ligand pattern designing, we find a suitable nanoparticle candidate with a specific polymer coating pattern for drug delivery. These findings provide useful guidelines for the molecular design of patterned NPs for controllable cell penetrability and help establish qualitative rules for the organization and optimization of copolymers ligands for desired drug delivery.

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Section: Introductionmentioning

confidence: 99%

Designing Nanoparticle Translocation through Cell Membranes by Varying Amphiphilic Polymer Coatings

2015

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“…One of the most important factors that influences drug loading is the drug's solubility in the micelle core compared with its solubility in water. Other influencing factors are the total molecular weight, the molecular weight of the corona‐forming block, and the preparation method by which the drug is loaded . The total molecular weight and molecular weight of the corona‐forming block will influence the aggregation number and the size of the particles, which in turn will influence the loading .…”

Section: Introductionmentioning

confidence: 99%

Tuning loading and release by modification of micelle core crystallinity and preparation

Glavas

Odelius

Albertsson

2015

Polymers for Advanced Techs

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Controlling and tuning the loading and release of incorporated drugs are vital parts of the advancement of drug delivery systems. Micelle systems that use core crystallinity to tune the loaded amount of hydrophobic molecules as well as their released amount were therefore developed. The conductive and electroactive aniline pentamer was incorporated into poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles with semi-crystalline cores and poly(ethylene glycol)-poly(ε-decalactone) (PEG-PεDL) micelles with amorphous cores. The difference in core crystallinity of the two micelle systems gave rise to highly different loading capacities and release rates. The loading capacity was strongly dependent on the core crystallinity, and the amorphous PEG-PεDL micelles had almost twice as high loading capacity as the semi-crystalline PEG-PCL micelles. In addition, the loading capacity was highly influenced by the loading procedure. The dependence on core crystallinity was also evident for the release of the aniline pentamer. The release occurred faster for the PEG-PεDL micelles with amorphous cores compared with the PEG-PCL micelles with semi-crystalline cores. The use of just these two systems gave us the ability to tune the released amount and rate, and a combination of these systems can enable access to a wide range of release profiles, thereby being available to a variety of drug delivery applications.

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“…MSD is the distance for beads move from one position to the next in a defined time span, defined as

M S D = 1 / N {\sum_{i = 1}^{N} true| r_{i} (t) - r_{i} (0) true|}^{2}

and calculated also in the Mesocite module of Materials Studio 5.5 software. To get the diffusion coefficient of a particle, the gradient of the MSD was taken following

D = (1 / 6 N) \lim t_{t \to \infty} (d / d t) {\sum_{i - 1}^{N} true| r_{i} (t) - r_{i} (0) true|}^{2}

, where

r_{i}

denotes the position vector of

i

the bead,

N

is the number of statistical beads . The diffusion coefficient of H 2 O, PEI, PAH‐Cit, and siRNA calculated through the MSD of polymers is 1.72 × 10 −8 , 6.00 × 10 −10 , 9.40 × 10 −9 , and 9.67 × 10 −10 m 2 /s, respectively, which agrees in magnitude with reported values.…”

Section: Resultsmentioning

confidence: 99%

Dissipative particle dynamic simulation on the assembly and release of siRNA/polymer/gold nanoparticles based polyplex

Xie

et al. 2017

AIChE Journal

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Dissipative particle dynamics simulation is used to reveal the loading/release of small interfering RNA (siRNA) in pH‐sensitive polymers/gold nanoparticles (AuNPs) polyplex. The conformation dynamics of these polyplex at various Au/siRNA mass ratios, the original AuNPs sizes, polymer types, and pH values are simulated and compared to experimental results. At neutral conditions (pH = 7.4), spherical micelles with a multilayer structure are formed in siRNA/polyethyleneimine/cis‐aconitic anhydride functionalized poly(allylamine)/polyethyleneimine/11‐mercaptoundecanoic acid‐gold nanoparticle (siRNA/PEI/PAH‐Cit/PEI/MUA‐AuNP) polyplex. Large polyplex are obtained with high Au/siRNA mass ratio and/or small original AuNPs size. The release dynamics of siRNA from AuNPs‐polyplex systems were also simulated in the intracellular environment (pH = 5.0). A swelling‐demicellization‐releasing mechanism is followed while the release of siRNA is found much faster for polyplex involving charge‐reversal PAH‐Cit. These findings are qualitatively consistent with the experimental results and may provide valuable guidance in later design and optimization of delivery carriers for siRNA or other molecule probes. © 2017 American Institute of Chemical Engineers AIChE J, 64: 810–821, 2018

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Drug Release from pH-Sensitive Polymeric Micelles with Different Drug Distributions: Insight from Coarse-Grained Simulations

Cited by 67 publications

References 53 publications

Designing Nanoparticle Translocation through Cell Membranes by Varying Amphiphilic Polymer Coatings

Designing Nanoparticle Translocation through Cell Membranes by Varying Amphiphilic Polymer Coatings

Tuning loading and release by modification of micelle core crystallinity and preparation

Dissipative particle dynamic simulation on the assembly and release of siRNA/polymer/gold nanoparticles based polyplex

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