Real-Time Monitoring of Doxorubicin Release from Hybrid Nanoporous Anodic Alumina Structures

This work demonstrates an advanced approach to fabricate Hybrid nanoporous anodic alumina gradient-index filters (Hy-NAA-GIFs) through a heterogeneous anodization process combining sinusoidal current-density anodization and constant potential anodization. As a result, the hybrid structure obtained reveals a single photonic stopband (PSB), which falls within the absorption region of the drug molecule and the intensity of the spectrum that are far from such absorption range. The prepared structures were loaded with the doxorubicin (DOX) drug through the drop-casting method, which allows for evaluating the maximum reflectance of the relative height of the PSB with the average reflectance of the spectrum intensity. Thereafter, this property has been applied in a flow cell setup connected to a reflectance spectrophotometer where different drug-loaded samples were placed to study the behavior and kinetics of the drug release in real-time by varying two parameters, i.e., different pore length and flow rates. As such, obtained results were analyzed with a model that includes a sum of two inverted exponential decay functions with two different characteristic time releases. Overall, this study opens up several possibilities for the Hy-NAA-GIFs to study the drug kinetics from nanoporous structures.

Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

This works deals with analysis of properties of a carbon nanotube, the tips of which were functionalized by short cytosine-rich fragments of ssDNA. That object is aimed to work as a platform for storage and controlled release of doxorubicin in response to pH changes. We found that at neutral pH, doxorubicin molecules can be intercalated between the ssDNA fragments, and formation of such knots can effectively block other doxorubicin molecules, encapsulated in the nanotube interior, against release to the bulk. Because at the neutral pH, the ssDNA fragments are in form of random coils, the intercalation of doxorubicin is strong. At acidic pH, the ssDNA fragments undergo folding into i-motifs, and this leads to significant reduction of the interaction strength between doxorubicin and other components of the system. Thus, the drug molecules can be released to the bulk at acidic pH. The above conclusions concerning the storage/release mechanism of doxorubicin were drawn from the observation of molecular dynamics trajectories of the systems as well as from analysis of various components of pair interaction energies.

Mass transfer of anti-cancer drug delivery to brain tumours by a multiple emulsion-based implant

The advanced use of a pH-responsive biomaterial-based injectable liquid implant for effective chemotherapeutic delivery in glioblastoma multiforme brain (GBM) tumour treatment is presented. As an implant, we proposed a water-in-oil-in-water multiple emulsion with encapsulated doxorubicin. The effectiveness of the proposed therapy was evaluated by comparing the cancer cell viability achieved in classical therapy (chemotherapeutic solution). The experimental study included doxorubicin release rates and consumption for two emulsions differing in drop sizes and structures in the presence of GBM-cells (LN229, U87 MG), and a cell viability. The results showed that the multiple emulsion implant was significantly more effective than classical therapy when considering the reduction in cancer cell viability: 85% for the emulsion-implant, and only 43% for the classical therapy. A diffusion-reaction model was adapted to predict doxorubicin release kinetics and elimination by glioblastoma cells. CFD simulations confirmed that the drug release kinetics depends on multiple emulsion structures and drop sizes.

AMD3100-tagged nano-gold as a targeting nanocarrier for delivery of doxorubicin into lung cancer cells

Doxorubicin (DOX) is widely used as a traditional chemotherapy drug in tumor treatment, but its dose-dependent side effects make it susceptible to acquired resistance. CXCR4 is a chemokine receptor that has high expression in many cancers, including lung cancer. In this work, we studied the possibility of using CXCR4 antagonist, AMD3100, as a targeting molecule to targeted delivery of DOX to CXCR4 expressing lung cancer cells through conjugated gold nanoparticles (Au NPs). DOX was intercalated inside the pH-responsive doublestrand DNA (dsDNA) and then conveniently loaded onto the Au NPs. The CXCR4 antagonist, AMD3100, was bonded with LA-PEG, and then conjugated to the surface of Au-S bond. The doxorubicin release from AuNPs@DOX@AMD3100 NPs was in a pH-dependent model, and specificity of AuNPs@DOX@AMD3100 nanoparticle was verified by using free DOX and Au@DOX NPs as control. Results in this work not only confirmed the possibility of using AMD3100 as a targeting ligand for tumor-targeted treatment, but also suggested that the non-toxic Au NPs is a prospect nanocarrier for target design of cancer therapy.

NIPAM/PEG/ MoS2 Nanosheets for Dual Triggered Doxorubicin Release and Combined Chemo-photothermal Cancer Therapy

Introduction: Among different 2-D nanostructures, molybdenum disulfide (MoS2) have shown a great potential as a good candidate in drug delivery systems. However, their biocompatibility and water dispersibility are main issues for these purposes. With the aim of improving the MoS2 dispersibility, a novel drug delivery system based on polymer modified MoS2 nanosheets was successfully prepared and characterized. Methods: In this study, MoS2 nanosheets were prepared using a simple oleum treatment exfoliation approach and then modified by grafting thermos-responsive polymer N- isopropylacrylamide (NIPAM) and poly ethylene glycol (PEG). The structural and morphological properties of the MoS2/NIPAM/ PEG nanosheets were characterized via scanning electron microscopy (SEM), X- ray diffraction (XRD), Fourier- transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA/DSC). Initially, the adsorption behavior of the grafted nanoadsorbent was assessed for sorption of doxorubicin as an anticancer drug model. The influence of various parameters such as pH, temperature, and contact time was evaluated. Different kinetic and isotherm models were employed to investigate the DOX adsorption mechanism. Results: The obtained results revealed that the DOX adsorption onto the MoS2/NIPAM/ PEG followed the Langmuir isotherm and pseudo-second-order models. In the next step, polymer grafted MoS2 nanosheets were used as thermos-sensitive drug nanocarriers for near-infrared (NIR) photothermal therapy. The combination of chemotherapy and photothermal therapy was also investigated which indicated a remarkable improvement of cell apoptotic rate, compared to monotherapy. Also, MTT assays showed that the MoS2/NIPAM/ PEG have high biocompatibility. Conclusion: The novel thermo- responsive MoS2/NIPAM/ PEG showed great potential for targeted and controlled drug delivery.