Modeling in Biopharmaceutics, Pharmacokinetics and Pharmacodynamics

Macheras, Panos; Iliadis, Athanassios

doi:10.1007/978-3-319-27598-7

Cited by 85 publications

(66 citation statements)

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“…The results presented in this report are strictly based on modeling and computation, which provides an ideal environment for systematic studies using well-controlled parameters and a userdefi ned complexity that can be gradually adapted. [ 64,65 ] Pure modeling and simulation is a deliberate choice of ours as direct experimental studies currently are not able to isolate and eliminate the infl uence of nanoparticle administration (i.e., pipetting) and nanoparticle detection. Most methods developed for detecting and quantifying nanoparticles are based on chemical elementary analysis [e.g., ICP techniques, [ 66,67 ] optical spectroscopy (e.g., absorption, [ 68 ] fl uorescence, [ 69 ] and vibrational [ 70,71 ] spectroscopy) , magnetic properties of the nanoparticle itself (e.g., superconducting quantum interference technique), [ 72 ] a molecular probe associated to the NPs, or neutron activation (e.g., radiolabeling techniques)].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle Polydispersity Can Strongly Affect In Vitro Dose

Rodríguez‐Lorenzo

Rothen‐Rutishauser

Petri‐Fink

et al. 2014

Part & Part Syst Charact

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When nanomaterials meet the biological world, the cellular interaction of nanoparticles is routinely assessed in in vitro systems. Establishing doseresponse relationships requires that the dose of nanoparticles delivered to the cell is accurate and precise. Nanoparticles as such or coated with high molecular-weight compounds are rarely uniform and the infl uence of heterogeneity, including polydispersity both in size and mass density, on the delivered dose is never studied before. Furthermore, a probabilistic term describing particle adherence to cells is introduced and the importance is discussed. By tracing the movement of discrete particles via modeling, it is found that the infl uence of heterogeneity cannot be neglected when the average particle size promotes settling over diffusion. However, the infl uence of polydispersity on the delivered cellular dose is less critical for particulate systems whose mean size promotes diffusion. The infl uence of a non-instantaneous particle association to the cell is negligible for particles whose motion is dominated by settling, but it is relevant for small particles whose motion is governed by diffusion.at least three elementary processes that are relevant for in vitro dose: (i) delivery of NPs to the cell, (ii) adherence to the cell membrane, and (iii) internalization. Any of these processes can be a rate-limiting factor. Awareness concerning the peculiarities of NP transport in fl uids and the relevance to liquid-based in vitro assays is on the rise, as shown by the steadily increasing number of research papers adopting the concept of particokinetics proposed by Teeguarden et al. [ 20,25 ] for interpreting dose-response curves. The concept of particokinetics, describing uniform particles, [ 20,25 ] challenges the still-reigning paradigm that the dose to which adherent cells are exposed to at the bottom of the cell-culture dish is proportional to the concentration of NPs in the suspension. However, the concentration of NPs in suspension defi nes only the administered dose, and the above paradigm is strictly valid only when all NPs in the suspension have completely settled, in which case the delivered dose is equal to the administered dose. The ultimate fate of NPs in a fl uid is eventually dictated by its mass density, i.e., NPs will settle if their mass density is greater than that of the fl uid. The impact of NP size and mass density on transport has been known for a long time [26][27][28][29] : in general, sedimentation is dominant for large NPs of "higher" mass density, while diffusion dominates the transport for small NPs of "lower" mass density. The kinetics of a particle is quantifi ed by the diffusion coeffi cient (the Stokes-Einstein equation and the settling velocity, Stokes' law). [ 26 ] Depending on (i) the hydrodynamic radius of the NPs, (ii) the mass density difference between the particle and the fl uid, (iii) the concentration of NPs in the colloidal suspension, (iv) the total volume of the colloidal suspension administrated to the cell culture, and (v...

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Section: Introductionmentioning

confidence: 99%

Nanoparticle Polydispersity Can Strongly Affect In Vitro Dose

Rodríguez‐Lorenzo

Rothen‐Rutishauser

Petri‐Fink

et al. 2014

Part & Part Syst Charact

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“…Observing that the particles are in direct contact with the capillary wall, we assume that the drug release rate to the interstitial volume per unit capillary surface is determined by the combination of the flux delivered by a single particle with the density of particles adhering to the wall. Determining the release profile of a single (spherical) loaded particle is a well studied problem in pharmacology . Here, following , we define it using a power law model with saturation,

\frac{q (t)}{q_{\infty}} = \frac{t^{b}}{t^{b} + normalΥ}, q_{\infty} = c_{np}^{*} V_{np}, then q (t) = \frac{t^{b}}{t^{b} + normalΥ} c_{np}^{*} V_{np},

where q ( t ) is the amount of drug released and q ∞ is the total drug load of a nanoparticle, given by the total drug concentration inside the nanoparticle,

c_{np}^{*}

(where * denotes an unspecified drug loaded on the particles), multiplied by the nanoparticle volume V n p .…”

Section: Methodsmentioning

confidence: 99%

A computational model of drug delivery through microcirculation to compare different tumor treatments

Cattaneo

Zunino

2014

Numer Methods Biomed Eng

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Starting from the fundamental laws of filtration and transport in biological tissues, we develop a computational model to capture the interplay between blood perfusion, fluid exchange with the interstitial volume, mass transport in the capillary bed, through the capillary walls and into the surrounding tissue. These phenomena are accounted at the microscale level, where capillaries and interstitial volume are viewed as two separate regions. The capillaries are described as a network of vessels carrying blood flow. We apply the model to study drug delivery to tumors. The model can be adapted to compare various treatment options. In particular, we consider delivery using drug bolus injection and nanoparticle injection into the blood stream. The computational approach is suitable for a systematic quantification of the treatment performance, enabling the analysis of interstitial drug concentration levels, metabolization rates and cell surviving fractions. Our study suggests that for the treatment based on bolus injection, the drug dose is not optimally delivered to the tumor interstitial volume. Using nanoparticles as intermediate drug carriers overrides the shortcomings of the previous delivery approach. This work shows that the proposed theoretical and computational framework represents a promising tool to compare the efficacy of different cancer treatments.

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“…For spherical-shaped samples, the n value lower than 0.43 was correlated to Fickian diffusion, whereas n value between 0.43 and 0.85 indicated the combined release mechanism. 68,69 The value of n 5 0.411 obtained from drug release occurred for 24 h from SA-loaded LMWC-B.8 which only involved diffusion did not best describe the release mechanism of the drug from a polymeric carrier like LMWC-B.8. From Table V, the data showed that Korsmeyer-Peppas model provided good fitting to < 80% of the drug release from SA-loaded LMWC-B.8 occurred during the first 14 h, as this suggested that the release of SA from this system (n 5 0.502) was not only governed by diffusion, but also included polymer swelling.…”

Section: In Vitro Release Studymentioning

confidence: 98%

Encapsulation of salicylic acid in acylated low molecular weight chitosan for sustained release topical application

Tiew

Misran

2017

J of Applied Polymer Sci

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Acylated low molecular weight chitosan was used to encapsulate salicylic acid (SA) for sustained release in topical delivery. Chitosan nanoparticles were prepared from the depolymerization of commercial chitosan and further acylated with short alkyl chains. The successful acylation of butyryl chitosan [low molecular weight chitosan (LMWC)‐B] were proved by Fourier transform infrared (FTIR) and 1H‐NMR. Successful encapsulation of SA was observed by the shift of amide I band from 1648 cm−1 in LMWC‐B to 1641–1633 cm−1 in SA‐loaded LMWC‐B in FTIR analysis, which further confirmed with the size increment from dynamic light scattering and transmission electron microscopy analyses by comparing its unencapsulated LMWC‐B. SA release from LMWC‐B studied by Franz diffusion experiment followed Korsmeyer–Peppas model where the release component n value (0.502) indicated diffusion and polymer swelling were involved in release mechanism. The slow release study of SA showed the acylated chitosan exhibited sustained release property toward SA. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45273.

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Modeling in Biopharmaceutics, Pharmacokinetics and Pharmacodynamics

Cited by 85 publications

References 0 publications

Nanoparticle Polydispersity Can Strongly Affect In Vitro Dose

Nanoparticle Polydispersity Can Strongly Affect In Vitro Dose

A computational model of drug delivery through microcirculation to compare different tumor treatments

Encapsulation of salicylic acid in acylated low molecular weight chitosan for sustained release topical application

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