Novel thermo/pH sensitive nanogels composed from poly(N-vinylcaprolactam) for controlled release of an anticancer drug, (original) (raw)
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Journal of Controlled Release, 1995
Modified diffusion equations with a time-dependent diffusion coefficient were derived to formulate the kinetics of drug release from a quickly degradable matrix. To compare the theoretical equations with experimental observation, microspheres containing aclarubicin hydrochloride (ACR) were prepared by the solvent evaporation method using DL-lactic acid (LA) oligomers with different weight-average molecular weights ranging from 1,900 to 9,600. ACR release profiles from the LA oligomer microspheres were apparently of quasi-zero order, showing no burst effect during the whole duration of release, unless the molecular weight of LA oligomers was as low as a few thousand. The early stage of drug release from the LA oligomer microspheres was well explained in terms of Fickian diffusion and the apparent initial diffusion coefficient could be determined as a function of the molecular weight of LA oligomer. The diffusion coefficient decreased with time as a result of degradation of the matrix. It was concluded that the newly derived equations were applicable for the drug release from the biodegradable matrix such as DL-LA oligomers.
Prediction of the mutual diffusion coefficient for controlled drug delivery devices
Computers Chemical Engineering, 2012
Diffusion coefficients of drugs in polymers were predicted using models based on modified free volume theory of diffusion. The descriptors used were chosen to uniquely relate the structure with desired properties. Model parameters were obtained using quantitative structure property relationships (QSPRs) developed using multiple linear regression and artificial neural networks with Bayesian regularization. Viability of the approach was established by predicting solvent diffusion coefficient in polymer for four polymer-solvent systems (polystyrene-toluene, polyvinylacetate-toluene, polystyrene-ethylbenzene and polystyrene-tetrahydrofuran) and comparing with the experimental values. The model was subsequently used on three polymer-drug systems (paclitaxel-polycaprolactone, hydrocortisone-polyvinylacetate and procaine-polyvinylacetate). The predicted diffusion coefficient for Paclitaxel-Polycaprolactone was used to study the release of Paclitaxel from Polycaprolactone under perfect sink condition. It is envisaged that the proposed model could be used in a reverse engineering framework to select polymers for designing the optimally controlled drug release devices.
Understanding Drug Release Data through Thermodynamic Analysis
Materials (Basel, Switzerland), 2017
Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas-Sahlin and Higuchi mod...
Analyzing Drug Release Kinetics from Water-Soluble Polymers
Industrial & Engineering Chemistry Research, 2019
The ability to develop predictive mathematical models of therapeutic release from pharmaceutical formulations has enormous potential to enhance our understanding of such systems and improve the controlled release of the payload. The current work describes the development and testing of a onedimensional model of drug transport from amorphous, swelling/dissolving polymers. Model parameters such as the diffusivities of water and drug, the initial loading of the drug, the polymer dissolution rate, drugpolymer interactions, and the tablet thickness were varied, demonstrating the ability to tune the release to be controlled by either drug diffusion or polymer chain disentanglement. In addition, predictions of the concentration profiles of water and drug within the gel layer, the locations of the erosion and swelling boundaries, and gel layer thickness were obtained for diffusion-and disentanglement-controlled release. To highlight the generalizability of this model, multiple parameters were varied, and it was shown that increasing the diffusivities of water and drug and the initial drug loading and decreasing the polymer dissolution rate sufficiently resulted in diffusion-controlled release. The model was fit to experimental data for a model tablet system comprising of sodium diclofenac entrapped in a poly(vinyl pyrrolidone) matrix and yielded physically meaningful values of the model parameters. The work presented here demonstrates the predictive power of the model for rapid and rational design of future pharmaceutical formulations for controlled drug delivery.
Biomolecules
The goal of this work was to comprehensive study the transport properties of controlled-release systems for the safe and reliable delivery of drugs. Special emphasis has been placed on the measurement of the diffusion of drugs, alone or in combination with carrier molecules for enhanced solubility and facilitated transport. These studies have provided detailed comprehensive information-both kinetic and thermodynamic-for the design and operation of systems for the controlled release and delivery of drugs. Cyclodextrins are among the most important carriers used in these systems. The basis for their popularity is the ability of these materials to solubilize poorly soluble drugs, generally resulting in striking increases in their water solubilities. The techniques used in these investigations include pulse voltammetry, nuclear magnetic resonance (NMR) and Raman spectroscopy, ultrasonic relaxation, and dissolution kinetics. Transport in these systems is a mutual diffusion process involving coupled fluxes of drugs and carrier molecules driven by concentration gradients. Owing to a strong association in these multicomponent systems, it is not uncommon for a diffusing solute to drive substantial coupled fluxes of other solutes, mixed electrolytes, or polymers. Thus, diffusion data, including cross-diffusion coefficients for coupled transport, are essential in order to understand the rates of many processes involving mass transport driven by chemical concentration gradients, as crystal growth and dissolution, solubilization, membrane transport, and diffusion-limited chemical reactions are all relevant to the design of controlled-release systems. While numerous studies have been carried out on these systems, few have considered the transport behavior for controlled-release systems. To remedy this situation, we decided to measure mutual diffusion coefficients for coupled diffusion in a variety of drug-carrier solutions. In summary, the main objective of the present work was to understand the physical chemistry of carrier-mediated transport phenomena in systems of controlled drug release.
Hemijska industrija, 2012
The aim of this paper is to propose equations for the diffusion of drugs for investigated drug/hydrogel systems using the parameters affecting the transport of drug through poly-(2-hydroxyethylmethacrylate/itaconic acid) (P(HEMA/IA)), poly(2-hydroxyethylacrylate/itaconic acid) (P(HEA/IA)), and poly(2-hydroxyethylmethacrylate/poly(alkyleneglycol) (meth)acrylates) (P(HEMA/BIS)) copolymeric hydrogels. Different monomer types, as well as the variable content of some components in hydrogel composition (the amount of ionizable comonomer (IA) and different type of nonionic poly(alkyleneglycol) (meth)acrylates), ultimately defined the pore size available for drug diffusion. The hydrogels synthesized ranged from nonporous to microporous, based on the classification in accordance to the pore size, and could be classified as hydrogels that contain ionic groups and hydrogels without ionic groups. The drugs selected for this study are bronchodilators-theophylline (TPH), fenethylline hydrochloride (FE), and antibiotic cephalexin (CEX). Results of in vitro drug release tests defined the release systems based on the drug type, as well as the type of hydrogel used. The diffusion coefficient of drugs and the restriction coefficient, λ, defined as the ratio of solute to "pore" radius (r s /r ζ ) that describes the ease of drug release from the gels, were used as factors that govern the release process.
Diffusion and mathematical modeling of release profiles from nanocarriers
International journal of …, 2006
The aim of this work was to establish models and to differentiate the kinetic release behavior of drug models from nanocapsules, nanoemulsion and nanospheres by physico-chemical characterization and release experiments. SAXS analysis showed that the polymer is organized in the nanocapsules, while in the nanospheres the sorbitan monostearate is organized and acts as an impurity of the poly(-caprolactone) suggesting that constituents in these nanocarriers are differently organized. Formulations presented particle sizes ranging from 178 to 297 nm, probe content from 0.981 to 0.997 mg/mL, pH values from 4.90 to 5.10 and zeta potential from −37.9 to −51.9 mV. The kinetic experiments showed that the nanostructures present similar behaviors when the probe is adsorbed on the nanocarriers (indomethacin-loaded formulations). However, when the probe is entrapped within the nanocarriers (indomethacin ethyl ester-loaded formulations), nanocapsules, nanospheres and nanoemulsion presented different kinetic behaviors. Mathematical modeling of the release profiles was conducted, showing that the presence of the polymer increases the half-lives of the burst phases (5.9, 4.4 and 2.7 min) while the presence of the oil increases the half-lives of the sustained phases (288.8, 87.7 and 147.5 min) for nanocapsules, nanospheres and nanoemulsion, respectively.
European Journal of Pharmaceutics and Biopharmaceutics, 2009
Different types of ethylcellulose-based mini-matrices were prepared by hot-melt extrusion and thoroughly characterized in vitro. Metoprolol tartrate was used as model drug, and various amounts and types of polyethylene glycol (PEG)/polyethylene oxide (PEO) were added as release rate modifiers. Based on the experimental results, appropriate mathematical theories were identified/developed, allowing for a better understanding of the underlying drug release mechanisms. For instance, it could be shown that at high initial PEG/PEO contents and/or intermediate initial PEG/PEO contents of low molecular weight, drug diffusion with time-and position-independent diffusivities is predominant. In contrast, at low initial PEG/PEO contents and intermediate initial PEG/PEO contents of high molecular weight, the time-and position-dependent dynamic changes in the matrix porosities significantly affect the conditions for drug and PEG/PEO diffusion. These dynamic changes must be taken into account in the mathematical model. Importantly, the proposed theories are mechanistic realistic and also allow for the quantitative prediction of the effects of the device design on the resulting drug release patterns. Interestingly, these quantitative predictions could be confirmed by independent experiments. Furthermore, Raman spectroscopy allowed for the determination of the resulting drug concentration-position profiles within the mini-matrices as a function of time and confirmed the theoretical predictions.
This study involves the synthesis of a new silica-based colloidal hybrid system. In this new hybrid system, poly (ethylene glycol) (PEG) and thermo-sensitive amphiphilic biocompatible poly (vinyl pyrrolidone) (PVP) were used to create suitable storage for hydrophobic drugs. The possibility of using variable PVP/PEG molar ratios to modulate drug release rate from silica nanoparticles was a primary goal of the current research. In addition, an investigation of the drug release kinetic was conducted. To achieve this, silica nanoparticles were synthesized in poly (ethylene glycol) (PEG) and poly (vinyl pyrrolidone) (PVP) solution incorporated with enrofloxacin (EFX) (as a model hydrophobic drug), using a simple synthetic strategy of hybrid materials which avoided waste and multi-step processes. The impacts of PVP/PEG molar ratios, temperature, and pH of the release medium on release kinetic were investigated. The physicochemical properties of the drug-loaded composites were studied by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In vitro drug release studies demonstrated that the drug release rate, which was evaluated by analyzing the experimental data with seven kinetic models in a primarily non-Fickian diffusion-controlled process, aligned well with both Ritger-Peppas and Sahlin-Peppas equations.