Tomasz Panczyk

Carbon nanotubes for delivery of small molecule drugs.

In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous attention as promising nanocarriers, owing to their distinct characteristics, such as high surface area, enhanced cellular uptake and the possibility to be easily conjugated with many therapeutics, including both small molecules and biologics, displaying superior efficacy, enhanced specificity and diminished side effects. While most CNT-based drug delivery system (DDS) had been engineered to combat cancers, there are also emerging reports that employ CNTs as either the main carrier or adjunct material for the delivery of various non-anticancer drugs. In this review, the delivery of small molecule drugs is expounded, with special attention paid to the current progress of in vitro and in vivo research involving CNT-based DDSs, before finally concluding with some consideration on inevitable complications that hamper successful disease intervention with CNTs.

The Langmuirian Adsorption Kinetics Revised: A Farewell to the XXth Century Theories?

A brief historical review of the development of the theoretical approaches to the kinetics of gas adsorption/desorption on/from the solid surfaces is presented. The attention is focused on new approaches, challenging the classical theories based on the ideas of Absolute Rate Theory (ART). These new approaches relate the adsorption/desorption kinetics to the chemical potentials of the molecules in the gas and adsorbed states. Among them the so-called Statistical Rate Theory (SRT) has the most rigorous theoretical foundations. That new approach predicts that depending on experimental conditions one can have a variety of kinetic equations corresponding to the Langmuir equilibrium adsorption isotherm.

In vivo biodistribution of platinum-based drugs encapsulated into multi-walled carbon nanotubes.

Carbon nanotubes (CNTs) are promising drug delivery systems due to their external functionalizable surface and their hollowed cavity that can encapsulate several bioactive molecules. In this study, the chemotherapeutic drug cisplatin or an inert platinum(IV) complex were entrapped inside functionalized-multi-walled-CNTs and intravenously injected into mice to investigate the influence of CNTs on the biodistribution of Pt-based molecules. The platinum levels in vital organs suggested that functionalized-CNTs did not affect cisplatin distribution, while they significantly enhanced the accumulation of Pt(IV) sample in some tissues (e.g. in the lungs, suggesting their potential application in lung cancer therapy) and reduced both kidney and liver accumulation (thus decreasing eventual nephrotoxicity, a typical side effect of cisplatin). Concurrently, CNTs did not induce any intrinsic abnormal immune response or inflammation, as confirmed by normal cytokine levels and histological evaluations. Therefore, functionalized nanotubes represent an efficient nano-carrier to improve accumulation of Pt species in targeted tissues/organs. From the clinical editor: In this preclinical study functionalized carbon nanotubes are reported to be safe and efficient for targeted delivery of platinum-containing compounds in rodents. Approaches like this may improve the treatment of specific cancers, since platinum based chemotherapies are commonly used, yet limited by toxicity and relatively poor target tissue concentration.

On the applicability of Arrhenius plot methods to determine surface energetic heterogeneity of adsorbents and catalysts surfaces from experimental TPD spectra.

Recovering adsorption energy distribution from experimental data belongs to most difficult problems of adsorption science. In the case when thermodesorption data are used as a source of information, that difficult problem is overcome by the common use of the Arrhenius plot methods. So, we decided to carry out an extensive model investigation to show, how reliable information concerning the surface energetic heterogeneity is obtained by using the Arrhenius plot methods. Like in our previous publications we have used the Statistical Rate Theory of Interfacial Transport to describe the adsorption/desorption kinetics. Our model investigations showed, that the Arrhenius plot methods, cannot provide reliable information about the surface energetic heterogeneity. Moreover, for strongly heterogeneous surfaces a linear relationship exists between the logarithm of the pre-exponential constant and the adsorption energy, for certain adsorption coverages. That kind of compensation effect has, so far, been ascribed to interactions between the adsorbed molecules. The failure of the popular Arrhenius plot method puts, as an urgent agenda, the development of reliable methods for recovering adsorption energy distribution from the thermodesorption data.

Phenomenological kinetics of real gas-adsorption-systems: Isothermal adsorption

Abstract Since Langmuir published the derivation of his famous adsorption isotherm equation in 1918, hundreds of papers on the kinetics of gas adsorption on solid surfaces have appeared in the world literature. Until the early fifties of the 20th century, these were mainly papers reporting on experimental studies of the kinetics of adsorption in various adsorption systems. Surprisingly, although the Langmuir isotherm described the adsorption equilibria fairly well, the related kinetic expressions generally failed to describe the adsorption kinetics. So, beginning in the early fifties, vigorous attempts were made to improve that kinetic approach based on ideas of the Absolute Rate Theory (ART). Since then, one has been able to see more progress on the theoretical side than in the related experimental studies. However, the vast majority of these papers treated hypothetical adsorption kinetics in virtual adsorption systems with well-defined surfaces. This was especially true in the case of the theoretical studies of isothermal adsorption kinetics. Certain progress was made in theoretical studies of the kinetics of thermodesorption, where the energetic heterogeneity of the real solid surfaces was demonstrated in an impressive way. Here, almost all the attempts to take energetic surface heterogeneity into account were based on a further generalization of the ART approach. In the early eighties a new family of fundamental approaches appeared, linking the rate of adsorption/desorption processes to the chemical potentials of the bulk and the adsorbed molecules. Among them the so-called Statistical Rate Theory (SRT) has received the most advanced theoretical attention. The new SRT approach has been generalized during recent years for the case of energetically heterogeneous surfaces. This has been done for both the isothermal kinetics and the kinetics of thermodesorption. So we have only two fundamental approaches which have been generalized for consideration of the kinetics of gas adsorption in the real systems, i.e. the ART and the SRT approaches. The purpose of the present review is to discuss the features of the adsorption kinetics in real adsorption systems, where the solid surface energetic heterogeneity is the main factor determining these features. For that purpose we will thoroughly analyze existing and possible future generalizations of both the ART and SRT approaches, taking this crucial physical factor into account. Next, we will apply the obtained theoretical expressions to quantitatively simulate the observed adsorption kinetics in real adsorption systems. Our study does not refer to the special case of the kinetics of sorption by porous media where the exchange of mass between the gas and the adsorbed phase may not be assumed as the only possible rate-controlling step.

Coadsorption of Doxorubicin and Selected Dyes on Carbon Nanotubes. Theoretical Investigation of Potential Application as a pH-Controlled Drug Delivery System.

This work shows results of a theoretical survey, based on molecular dynamics simulation, of potential applicability of doxorubicin coadsorption with various dyes molecules on/in carbon nanotubes as a drug delivery system. The central idea is to take advantage of the dyes charge distribution change upon switching the pH of the environment from neutral (physiological 7.4) to acidic one (∼5.5 which is typical for tumor tissues). This work discusses results obtained for four dye molecules revealing more or less interesting behavior. These were bromothymol blue, methyl red, neutral red, and p-phenylenediamine. All of them reveal pKa in the range 5-7 and thus will undergo protonation in that pH range. We considered coadsorption on external walls of carbon nanotubes and sequential filling of the nanotubes inner hollow space by drug and dyes. The latter approach, with the application of neutral red and p-phenylenediamine as blockers of doxorubicin, led to the most promising results. Closer analysis of these systems allowed us to state that neutral red can be particularly useful as a long-term blocker of doxorubicin encapsulated in the inner cavity of (30,0) carbon nanotube at neutral pH. At acidic pH we observed a spontaneous release of neutral red from the nanotube and unblocking of doxorubicin. We also confirmed, by analysis of free energy profiles, that unblocked doxorubicin can spontaneously leave the nanotube interior at the considered conditions. Thus, that system can realize pH controlled doxorubicin release in acidic environment of tumor tissues.

Sticking coefficient and pressure dependence of desorption rate in the statistical rate theory approach to the kinetics of gas adsorption. Carbon monoxide adsorption/desorption rates on the polycrystalline rhodium surface

The statistical rate theory (SRT) fundamental kinetic equation for the Langmuir model of adsorption reveals some features which are difficult to understand. These are the infinitely high adsorption rate for zero coverage limit, infinitely high desorption rate at full saturation of the surface and dependence of the desorption rate on the adsorbate pressure. These features do not allow for a correct formulation of such important physical parameters as sticking and initial sticking probabilities. In this work these peculiar features of the fundamental SRT kinetic equation are discussed and explained. It is shown that the non-physical behavior of the SRT kinetic equation follows from neglecting possible changes of adsorbate concentration near the adsorbing surface. A simple model accounting for the changes of adsorbate concentration close to the adsorbing surface is discussed. As a result, it was shown that application of even such a simple model leads to fully physical behavior of the SRT kinetic equation for the Langmuir model of adsorption. The model is used to build up equations describing the kinetics of adsorption/desorption of carbon monoxide on the energetically heterogeneous rhodium surface. The values of the parameters in these equations were determined from the analysis of equilibrium adsorption isotherms and from the description of experimental conditions. One additional parameter (having well defined limiting values) had to be adjusted in order to satisfactorily reproduce kinetic data. The experimental data used in this work were taken from the article by Yamada and Tamaru (T. Yamada and K. Tamaru, Surf. Sci., 1984, 138, L155).

Thermodesorption studies of energetic properties of nickel and nickel-molybdenum catalysts based on the statistical rate theory of interfacial transport

The new theoretical approach to adsorption/desorption kinetics, called the statistical rate theory of interfacial transport, is used to analyze quantitatively spectra of hydrogen thermodesorption from alumina-supported nickel and nickel-molybdenum catalysts. A new more accurate method is developed to calculate the distribution of the chemisorption energies on the surfaces of these two catalysts. The comparison of their adsorption energy distributions shows that the addition of molybdenum, changes relative mutual proportions of the four kinds of chemisorption sites existing on these catalysts surfaces. Changing these proportions is related to changing tendencies to coking formation and changing activities for methane steam reforming.

Self-assembly of molecular tripods in two dimensions: structure and thermodynamics from computer simulations

Controlled self-organization of molecular building blocks into low-dimensional ordered superstructures is a promising method of fabrication of functional materials with tunable physico-chemical properties. In this contribution we use the Parallel Tempering Monte Carlo simulation method to study the self-assembly of tripod molecules adsorbed on a triangular lattice being an analog of a graphite surface. In the adopted approach the molecules were assumed to be flat rigid C3-symmetric structures composed of a central segment connected with three n-membered arms. Our primary objective was to examine the effect of molecular size, n on the topology of the corresponding phase diagrams and to identify stable ordered phases with different morphologies. It was demonstrated that for the tripod molecules with sufficiently long arms (n > 1), the self-assembly leads to the formation of scalable chiral porous networks with hexagonal void spaces. For these systems the phase coexistence was found to be described by phase diagrams with the same overall topology. On the other hand, the simulations performed for the small tripods with n = 1 revealed the formation of compact patterns, resulting in a substantial change in the shape of the phase diagram. The insights from our theoretical investigations can be helpful in designing 2D self-assembled molecular architectures comprising C3-symmetric functional units.

Implicit solvent model for effective molecular dynamics simulations of systems composed of colloid nanoparticles and carbon nanotubes

In this paper we propose an implicit solvent model which can be used in molecular dynamics simulations of systems comprising colloid nanoparticles and carbon nanotubes. Such systems, due to finite nanometer sizes of both components cannot be accurately approximated by a smaller slab geometry and thus represent a particularly difficult case in terms of computer simulations. In particular, nanoparticle sizes of a few tens of nanometers lead to billions of solvent molecules in a simulation box and require very long cut-off distances which drastically increases computation time. To overcome this difficulty we develop an implicit solvent model based on Hamaker theory of dispersive interactions. The predictions of our model are verified by comparison with the exact model, involving all atoms and full description of pair interactions. The proposed model correctly predicts the work of adhesion and average configuration in colloid - carbon nanotube systems. Moreover, application of the Langevin dynamics reproduces the dynamic behaviour of the exact model either.