We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in-vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea. The implications of the work for optimizing the design of drug delivery vehicles are discussed.
In this work we investigate the use of nanoporous carrier as drug delivery systems for hydrophobic molecules. By studying a model system made of porous silicon loaded with beta-carotene, we unveil a fundamental limitation of these carriers that is due to heterogeneous nucleation that imposes a tradeoff between the amount of drug loaded and the reproducibility of the release. Nonetheless, such issue is an alternative and improved method, compared with the standard induction time, to monitor the formation of heterogenously nucleated aggregates.
We present a mechanistic model of drug release from a multiple emulsion into an external surrounding fluid. We consider a single multi-layer droplet where the drug kinetics are described by a pure diffusive process through different liquid shells. The multi-layer problem is described by a system of diffusion equations coupled via interlayer conditions imposing continuity of drug concentration and flux. Mass resistance is imposed at the outer boundary through the application of a surfactant at the external surface of the droplet. The two-dimensional problem is solved numerically by finite volum…
Efficient and non-invasive techniques of cargo delivery to biological cells are the focus of biomedical research because of their great potential importance for targeted drug therapy. Therefore, much effort is being made to study the characteristics of using nano-based biocompatible materials as systems that can facilitate this task while ensuring appropriate self-sealing of the cell membrane. Here, we study the effects of indentation and withdrawal of nanospear on phospholipid membrane by applying steered molecular dynamics (SMD) technique. Our results show that the withdrawal process directl…
Staphylococcus aureus responsible for nosocomial infections is a significant threat to the public health. The increasing resistance of S.aureus to various antibiotics has drawn it to a prime focus for research on designing an appropriate drug delivery system. Emergence of Methicillin Resistant Staphylococcus aureus (MRSA) in 1961, necessitated the use of vancomycin "the drug of last resort" to treat these infections. Unfortunately, S.aureus has already started gaining resistances to vancomycin. Liposome encapsulation of drugs have been earlier shown to provide an efficient method of microbial …
Computational Modeling of an MRI Guided Drug Delivery System Based on Magnetic Nanoparticle Aggregations for the Navigation of Paramagnetic Nanocapsules
Predicting the release performance of a drug delivery device is an important challenge in pharmaceutics and biomedical science. In this paper, we consider a multi-layer diffusion model of drug release from a composite spherical microcapsule into an external surrounding medium. Based on this model, we present two approaches that provide useful indicators of the release time, i.e. the time required for the drug-filled capsule to be depleted. Both approaches make use of temporal moments of the drug concentration versus time curve at the centre of the capsule, which provide useful insight into the…
We develop, analyse and numerically simulate a model of a prototype, glucose-driven, rhythmic drug delivery device, aimed at hormone therapies, and based on chemomechanical interaction in a polyelectrolyte gel membrane. The pH-driven interactions trigger volume phase transitions between the swollen and collapsed states of the gel.For a robust set of material parameters, we find a class of solutions of the governing system that oscillate between such states, and cause the membrane to rhythmically swell, allowing for transport of the drug, fuel and reaction products across it, and collapse, hamp…
Letter to the Editor Concerning "Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles"
We present a general mechanistic model of mass diffusion for a composite sphere placed in a large ambient medium. The multi-layer problem is described by a system of diffusion equations coupled via interlayer boundary conditions such as those imposing a finite mass resistance at the external surface of the sphere. While the work is applicable to the generic problem of heat or mass transfer in a multi-layer sphere, the analysis and results are presented in the context of drug kinetics for desorbing and absorbing spherical microcapsules. We derive an analytical solution for the concentration in …
New mixed cationic liposomes based on L-α-phosphatidylcholine and dihexadecylmethylhydroxyethylammonium bromide (DHDHAB) were designed to overcome the BBB crossing by using the intranasal route. Synthesis and self-assembly of DHDHAB were performed. A low critical association concentration (0.01 mM), good solubilization properties toward hydrophobic dye Orange OT and antimicrobial activity against gram-positive bacteria Staphylococcus aureus (MIC=7.8 μg.mL-1) and Bacillus cereus (MIC=7.8 μg.mL-1), low hemolytic activities against human red blood cells (less than 10%) were achieved. Conditions f…
Lipid-based drug delivery systems are considered as promising vehicles for hydrophobic drug compounds. Lipid distribution within the droplet can affect drug loading capacity in these carriers. It is extremely challenging to determine the nanostructure within these carriers through the implementation of the direct experimental methods due to the ultrafine size. Therefore, coarse grained molecular dynamics (MD) simulation was utilized to model different lipid-based nanoparticles of the diameter about 12 nm including solid lipid nanoparticles (SLN), nanoemulsion (NE), and nanostructured lipid car…
We propose two-dimensional organic poly(heptazine imide) (PHI) carbon nitride microparticles as light-driven microswimmers in various ionic and biological media. Their demonstrated high-speed (15-23 $μ$m/s) swimming in multi-component ionic solutions with concentrations up to 1 M and without dedicated fuels is unprecedented, overcoming one of the bottlenecks of previous light-driven microswimmers. Such high ion tolerance is attributed to a favorable interplay between the particle's textural and structural nanoporosity and optoionic properties, facilitating ionic interactions in solutions with …
One of the most important potential applications of self-propelled nano- and microdevices is targeted drug delivery. To realize this, biocompatible particles that can be guided collectively towards a target inside a patient's body are required. Acoustically propelled nano- and microparticles constitute a promising candidate for such biocompatible, artificial motile particles. The main remaining obstacle to targeted drug delivery by self-propelled nano- and microdevices is to also achieve a reliable and biocompatible method for guiding them collectively to their target. Here, we propose such a …
Thermoresponsive hydrogels have been studied intensively for creating smart drug carriers and controlled drug delivery. Understanding the drug release kinetics and corresponding transport mechanisms of nanoparticles (NPs) in a thermoresponsive hydrogel network is the key to the successful design of a smart drug delivery system. We construct a mesoscopic model of rigid NPs entrapped in a hydrogel network in an aqueous solution, where the hydrogel network is formed by cross-linked semiflexible polymers of PNIPAM. By varying the environmental temperature crossing the lower critical solution tempe…
Receptor-mediated endocytosis is an ubiquitous process through which cells internalize biological or synthetic nanoscale objects, including viruses, unicellular parasites, and nanomedical vectors for drug or gene delivery. In passive endocytosis the cell plasma membrane wraps around the "invader" particle driven by ligand-receptor complexation. By means of theory and numerical simulations, here we demonstrate how particles decorated by freely diffusing and non-mutually-interacting (ideal) ligands are significantly more difficult to wrap than those where ligands are either immobile or interact …
The study of the ability of drug molecules to enter cells through the membrane is of vital importance in the field of drug delivery. In cases where the transport of the drug molecules through the membrane is not easily accomplishable, other carrier molecules are used. Spherical fullerene molecules have been postulated as potential carriers of highly hydrophilic drugs across the plasma membrane. Here we report the coarse-grain molecular dynamics study of the translocation of C60 fullerene and its derivatives across a cell membrane modeled as a 1, 2-distearoyl-sn-glycero-3-phosphocholine (DSPC) …
