Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels

The investigations deal with mass transfer in simulated biomedical systems. The modification of classical diffusion chamber, sequential unit (SU) system, imitated different biomedical setups, boundary conditions. The experiments simulated: diffusion chamber (also with two barriers), transport through the membrane to the blood stream, transport from the stent eluting drug simultaneously to the vessel cells and to the blood stream. The concentrations of substances and the relative mass increases/decreases for SU systems indicate that the order of the curves follows the order of mass transfer resistances. The strong dependence of mass transfer rates versus type of diffusing substance was confirmed. The calculated drug fluxes, diffusion coefficients, permeation coefficients are convergent with literature. Permeation coefficients for complex sequential systems can be estimated as parallel connexion of constituent coefficients. Experiments approved functionality of the SU for investigations in a simulated biomedical system. Obtained data were used for numerical verification.

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“…The obtained results were consistent with the literature data (Giannola et al, 2007;Ansari et al, 2006;Serra et al, 2006).…”

supporting

confidence: 93%

Determination of diffusion coefficient and permeability through the barrier of substance in simulated biomedical systems

Adach

Kister

Skassa

et al. 2017

Chemical and Process Engineering

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“…Often the transport mechanism in this type of systems does not behave according to Fickian diffusion. In fact, the results obtained in experimental context support the previous sentence ( [6], [10], [25], [31], [33], [34], [36], [37], see also [35] and the references contained in the last paper). However, often we find in the literature mathematical models for percutaneous drug absorption considering the system vehicle-skin established by using Fick's law (see e.g.…”

supporting

confidence: 87%

Coupled vehicle–skin models for drug release

Barbeiro

Ferreira

2009

Computer Methods in Applied Mechanics and Engineering

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Please cite this article as: S. Barbeiro, J.A. Ferreira, Coupled vehicle-skin models for drug release, Comput. Methods Appl. Mech. Engrg. (2009), doi: 10.1016/j.cma.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT AbstractPercutaneous absorption of a drug delivered by a vehicle source is usually modeled by using diffusion Fick's law. In this case, the model consists in a system of partial differential equations of diffusion type with a compatibility condition on the transition boundary between the vehicle and the skin. Using this model, the fractional drug release in both componentsvehicle and skin -is proportional to the square root of the release time. Often experimental results show that the predicted drug concentration distribution in the vehicle and in the skin by the Fick's model does not agree with experimental data. In this paper we present a nonFickian mathematical model for the introduced percutaneous absorption problem. In this new model the Fick's law for the flux is modified by introducing a non-Fickian contribution defined with a relaxation parameter related to the properties of the components. Combining the flux equation with the mass conservation law, a system of integro-differential equations is established with a compatibility condition on the boundary between the two components of the physical model. The stability analysis is presented. In order to simulate the mathematical model, its discrete version is introduced. The stability and convergence properties of the discrete system are studied. Numerical experiments are also included.

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“…These indicate that DOX release was the synergistic effect of nanogel degradation and drug diffusion. 31,32 The dual-sensitivity-triggered DOX release behavior could be explained by the coordinated dual sensitivity.…”

Section: Drug Loading and Releasing Property Of Star Polymer Nanogelmentioning

confidence: 99%

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

Lou¹,

Zhang²,

Zhang³

et al. 2017

IJN

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A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC 50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy.

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Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels

Cited by 429 publications

References 37 publications

Determination of diffusion coefficient and permeability through the barrier of substance in simulated biomedical systems

Determination of diffusion coefficient and permeability through the barrier of substance in simulated biomedical systems

Coupled vehicle–skin models for drug release

Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

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