A promising dual-drug targeted delivery system in cancer therapy: nanocomplexes of folate-apoferritin-conjugated cationic solid lipid nanoparticles.

Various nano-sized protein and lipid complexes are being investigated as drug delivery systems. The encapsulation of more than one drug in a single nanocomplex carrier could enhance the therapeutic potency and afford synergistic therapeutic effects. In this study, we developed a novel protein-lipid nanocomplex as a controlled drug delivery system for two important cancer drugs, doxorubicin (DOX) and mitoxantrone (MTO). Apoferritin (AFr) functionalized with folic acid (FA) was used to encapsulate DOX to create the targeted protein nanocomplexes (TPNs). The second drug, MTO, was loaded into the cationic solid lipid nanoparticles (cSLN) to form the liposomal drug nanocomplex particles (MTO-cSLNs). Two complexes were then assembled by tight coupling through ionic interactions to obtain the final drug delivery system, the dual-targeted protein-lipid nanocomplexes (DTPLNs). UV-Vis and fluorescence spectroscopy were used for structural characterization of TPNs and DTPLNs. Transmission electron microscopy (TEM) was used for comprehensive analysis of the final DTPLNs. We confirmed that the DTPLNs display desired time-dependent and pH-dependent drug release behaviors. We also demonstrated the improved anti-cancer efficacy of DOX and MTO in their encapsulated DTPLNs as compared to their free forms. Our results provide promising prospects for the application of the DTPLNs as efficient drug delivery systems.

Evaluating the photodynamic therapy efficacy using 5-aminolevulinic acid and folic acid-conjugated bismuth oxide nanoparticles on human nasopharyngeal carcinoma cell line.

Selective accumulation of photosensitizers (PSs) into cancerous cells is one of the most important factors affecting photodynamic therapy (PDT) efficacy. 5-Aminolevulinic acid (5-ALA) is precursor of a strong PS, protoporphyrin-IX (Pp-IX); but it has poor permeability in lipophilic membrane of the cells due to its hydrophilic property. Therefore, establishment of an improved delivery strategy could highly affect on treatment outcome. Moreover, folate receptors (FRs) are overexpressed on the surface of many tumor cells. In the present work, targeting ligand folic acid (FA) and 5-ALA conjugated bismuth oxide nanoparticles (FA-5ALA-Bi2O3 NPs) were synthesized; and used in PDT against human nasopharyngeal carcinoma cells (KB cell line). The KB cells incubated with the synthesized NPs for 2 h; then illuminated using a custom-made red light LED lamp at the light dose of 26 J/cm2. MTT and caspase-3 activity assays were performed to evaluate the efficacy of treatment. Results showed that FR targeting ligand enables selective endocytosis of FA-5-ALA-conjugated NPs into KB cells. Improved internalization of 5-ALA into cells decreased the cell viability to about 50%, 65%, and 85% in the groups receiving FA-5ALA-Bi2O3 NPs, 5ALA-Bi2O3 NPs, free 5-ALA and subsequent PDT, respectively. Therefore, FA-5ALA-Bi2O3 NPs can significantly increase the cell killing effect of PDT.

Chitosan/gelatin as a new nano-carrier system for calcium hydroxide delivery in endodontic applications: Development, characterization and process optimization.

The main aim of this study is preparation, optimization and in vitro characterization of Chitosan/Gelatin nano-carriers (NCs) for calcium hydroxide (CH) to improve its therapeutic potential. The designed system can be used in the endodontic applications demanding a sustained release of calcium and hydroxyl ions. Modeling and optimization of CH loaded polymeric NCs were performed using response surface methodology (RSM) based on central composite surface statistical design. The effect of Chitosan concentration (0.1-1% w/v), Gelatin concentration (0.1-1% w/v) and CH concentration (0.05-0.4% w/v) on the particle size, polydispersity index (PDI), drug loading (DL) and encapsulation efficiency (EE) of CH loaded polymeric NCs were investigated. Optimized CH loaded polymeric NCs formulation which obtained using RSM showed spherical and smooth surface with a particle size of 292 nm, PDI of 0.32, DL of 88.8% and EE of 99%. Optimized formulation was evaluated for in vitro calcium ion release in phosphate buffer solution (PBS) at pH 7.4 for 14 days. The presence of hydrogen bonding and some intermolecular interactions between Chitosan/Gelatin polymeric materials were confirmed using Fourier transform infrared (FTIR) analysis. These interactions enable Chitosan/Gelatin NCs to load CH and maintain sustained release of Calcium ions from CH during experimental period.

Epirubicin-calf thymus DNA interaction: a comprehensive investigation using molecular docking, spectroscopy and fluorescent quantum dots.

Reviewing the mode of interaction between this kind of active pharmaceutical ingredients and DNA has received much more attention in current years. Anthracycline drugs such as Epirubicin are frequently used in cancer treatment for breast cancer treatment. In the present study, the Epirubicin -calf thymus DNA interaction was investigated by using spectroscopic, fluorimetric and molecular docking methods. Water-soluble quantum dots (QDs) with nanometric particle size fabricated and characterized by transmission electron microscope and photon correlation spectroscopy. The binding constant value and the free energy change for this interaction were obtained to be 3.00×106 M-1 and -42.26 kJ mol-1, using the spectroscopic method and docking investigations, respectively. Additionally, fluorescent thioglycolic acid-capped CdTe QDs were used for investigation of EPI and DNA interaction. Epirubicin as a quencher quenched the fluorescence of CdTe QDs after electrostatic adsorption on the surface of QDs. With the addition of DNA, EPI will be desorbed from the surface of CdTe QDs, inserted into the DNA. Subsequently, fluorescence changes of QDs were used for calculation of binding constant value, which was in good agreement with that obtained by the spectroscopic method. By the comparison of the achieved results, the intercalation mode of interaction between Epirubicin and DNA proved.

Folate Conjugated Hybrid Nanocarrier for Targeted Letrozole Delivery in Breast Cancer Treatment.

PURPOSE: Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment. METHODS: Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated. RESULTS: Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC50 value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozole entrapment on the drug bioavailability. CONCLUSIONS: The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.

The Role of Nanoparticle in Brain Permeability: An in-vitro BBB Model.

Membrane permeability and P-glycoprotein (P-gp) efflux system are regulating factors in the drug brain penetration. Recently, some drug delivery systems have been developed to overcome these limitations. In this study, Metoclopramid has been encapsulated in PLGA nanoparticles using the emulsification/solvent evaporation technique for in-viro evaluation of the effect of PLGA nanoparticles on BBB permeability. Subsequently, prepared nanoparticles were characterized using PCS, TEM, FT-IR, DSC and XRD techniques and in-viro cell permeability of optimum formulation was evaluated using MDCK cell line as BBB model. Data investigation showed that prepared nanoparticles have the entrapment efficiency of 50 %. PCS investigation showed that prepared nanoparticles have an average size of approximately 150 ± 14 nm and a relatively monodisperse distribution. TEM micrographs of the samples showed spherical shape and smooth surface with a particle size of nanometric range. Through DSC thermograms and XRD diffractograms analysis, it was demonstrated that there was no crystalline form of the drug in the loaded formulation. Moreover, our results showed that the greater crossing of metoclopramide in the form of nanoparticle in comparison with the free form. The widely used rhodamine-123 transport assay performed in the MDCK cells demonstrated the presence of P-glycoprotein in this model.