Microfluidic platform for synthesis and optimization of chitosan-coated magnetic nanoparticles in cisplatin delivery.

In this study, magnetic core/chitosan shell Nanoparticles (NPs) containing cisplatin were synthesized via cisplatin complexation with tripolyphosphate as the chitosan crosslinker using two different procedures: a conventional batch flow method and a microfluidic approach. An integrated microfluidic device composed of three stages was developed to provide precise and highly controllable mixing. The comparison of the results revealed that NPs synthesized in microchannels were monodisperse 104 ±â€¯14.59 nm (n = 3) in size with optimal morphological characteristics, whereas polydisperse 423 ±â€¯53.33 nm (n = 3) nanoparticles were obtained by the conventional method. Furthermore, cisplatin was loaded in NPs without becoming inactivated, and the microfluidic technique demonstrated higher encapsulation efficiency, controlled release, and consequently lower IC50 values during exposure to the A2780 cell line proving that microfluidic synthesized NPs were able to enter the cells and release the drug more efficiently. The developed microfluidic platform presents valuable features that could potentially provide the clinical translation of NPs in drug delivery.

Drug delivery to solid tumors with heterogeneous microvascular networks: Novel insights from image-based numerical modeling.

The present study examines chemotherapy by incorporating multi-scale mathematical modeling to predict drug delivery and its effects. This approach leads to a more-realistic physiological tumor model than is possible with previous approaches, as it obtains the capillary network geometry from an image, and also considers the tumor's necrotic core, drug binding, and cellular uptake. Modeling of the fluid flow and drug transport is then performed in the extracellular matrix. The results demonstrate a 10% drop in the fraction of killed cancer cells 69% rather than the 79% reported earlier for a tumor of similar geometry a more-accurate value. This study examines how tumor-related parameters including the necrotic core size and tumor size, and also drug-related parameters drug dosage, binding affinity of drug, and drug degradation can affect the delivery of the drug to solid tumors. Results indicate that concentration of drug are high in the tumor, low in normal tissue, and remarkably low in the necrotic core. Results also offer a treatment of tumors with smaller necrotic core. Tumor size, which implies the tumor progression, has a considerable impact on treatment outcomes, so to be more effective, treatment should be applied at a specific size of tumor. It is demonstrated that binding affinity of drugs to cell-surface receptors and drug dosage have significant impact on treatment efficacy, so they should be regulated based on a balanced quantification between maximum treatment efficacy and minimum side effects. On the other hand, considering the effects of drug degradation in the model has not significant effect on treatment efficacy. The findings of the present study provide insight into the mechanism of drug delivery to solid tumors based on analyzing the effective parameters and modeling how their behavior in the tumor microenvironment affects treatment efficacy.

Image-based spatio-temporal model of drug delivery in a heterogeneous vasculature of a solid tumor - Computational approach.

The solute transport distribution in a tumor is an important criterion in the evaluation of the cancer treatment efficacy. The fraction of killed cells after each treatment can quantify the therapeutic effect and plays as a helpful tool to evaluate the chemotherapy treatment schedules. In the present study, an image-based spatio-temporal computational model of a solid tumor is provided for calculation of interstitial fluid flow and solute transport. Current model incorporates heterogeneous microvasculature for angiogenesis instead of synthetic mathematical modeling. In this modeling process, a comprehensive model according to Convection-Diffusion-Reaction (CDR) equations is employed due to its high accuracy for simulating the binding and the uptake of the drug by tumor cells. Based on the velocity and the pressure distribution, transient distribution of the different drug concentrations (free, bound, and internalized) is calculated. Then, the fraction of killed cells is obtained according to the internalized concentration. Results indicate the dependence of the drug distribution on both time and space, as well as the microvasculature density. Free and bound drug concentration have the same trend over time, whereas, internalized and total drug concentration increases over time and reaches a constant value. The highest amount of concentration occurred in the tumor region due to the higher permeability of the blood vessels. Moreover, the fraction of killed cells is approximately 78.87% and 24.94% after treatment with doxorubicin for cancerous and normal tissues, respectively. In general, the presented methodology may be applied in the field of personalized medicine to optimize patient-specific treatments. Also, such image-based modeling of solid tumors can be used in laboratories that working on drug delivery and evaluating new drugs before using them for any in vivo or clinical studies.