Drug Delivery System For Photodynamic Therapy Research Articles

Zinc pthalocyanine loaded poly (lactic acid) nanoparticles by double emulsion methodology for photodynamic therapy against 9 L/LacZ gliosarcoma cells

Development delivery systems, such as nanoparticles, represent a growing area in biomedical research. Nanoparticles (NP) were prepared using a double-emulsion method to load zinc(II) phthalocyanine (ZnPc). NP were obtained using poly (lactic acid) (PLA). ZnPc is a second generation of photosensitizer used in photodynamic therapy (PDT). ZnPc loaded PLA nanoparticles (NPLA-ZnPc) were prepared by double-emulsion method, characterized and available in cellular culture. The mean nanoparticle size presented particle size was 384.7 ± 84.2 nm with polydispersity index (PDI) of 0.150 ± 0.015, and the encapsulation efficiency was of 83%. The nanoparticle formulations presented negative zeta potential values (−27.5 ± 1.0 mV), explaining their colloidal stability. ZnPc loaded nanoparticles maintain its photophysical behavior after encapsulation. Photosensitizer release from nanoparticles was sustained over 168 h with a biphasic ZnPc release profile. An in vitro phototoxic effect in range of 80% was observed in 9 L/LacZ gliosarcoma cells at laser light doses (10 J cm−2) with 3.0 µg mL−1 of NPLA-ZnPc. All the physical–chemical, photophysical and photobiological measurements performed allow us to conclude that ZnPc loaded PLGA nanoparticles is a promising drug delivery system for PDT.

Thermosensitive nanocomposite gel loaded zinc phthalocyanine for photodynamic therapy

The purpose of this work was first to propose a thermosensitive hydrogel incorporating Zn phthalocyanine loaded mixed micelles for drug delivery. The mixed micelles was prepared easily by dialysis method and the thermosensitive hydrogel was prepared by “cold method” using Pluronic F127 as hydrogel matrix. The properties of sol and gel transition caused by F127 temperature response enables the drug loaded micellar hydrogel(DLM-Gel) to gel in situ gelification upon injection providing long-term retention within the tumor. Sodium deoxycholate (SDC) and D-alpha tocopheryl polyethylene glycol succinate (TPGS) were utilized as micelles materials. Micelles resulted in a mean particle size around 106 nm, spherical morphology and loading efficiency up to 92%. The DLM-Gel displayed a three-dimensional network structure, which helps to stabilize ZnPc molecules because it can reduce the rotation and intermolecular collision of the ZnPc molecules, leading to the enhancement of fluorescence intensity and 1O2 generation. The production of 1O2 from DLM-Gel was more efficient than micelles under the same laser irradiation condition. The DLM-Gel was more photostable than free ZnPc and micelles in the timescale typically used in photodynamic therapy(PDT), only a small photobleaching event(16.91%) was observed after 20 min of light irradiation. Rheology studies demonstrated that DLM-Gel has the potential to be injected at room temperature and to adapt to the deformation of surrounding tissues during human motion. The in vitro drug release studies of DLM-Gel demonstrated slower drug release than mixed micelles. Phototoxicity experiments in A549 cells showed that DLM-Gel had significante toxicity.Therefore the injective micellar hydrogels is a potential drug delivery system for PDT.

Development of DNA polymer films as a drug delivery system for the treatment of oral cancer.

DNA polymer films (DNA-PFs) hold promise for use in drug delivery systems (DDS). In this study, the growth pattern of oral squamous cell carcinoma (OSCC) cells was evaluated on DNA-PFs incorporated with a photoactive compound chlorine aluminum phthalocyanine (DNA-PFs-AlClPc) and the efficacy of DNA-PFs-AlClPc as a DDS for photodynamic therapy (PDT) for the treatment of mucosal cancer. Flow cytometry was used to evaluate cell viability following application of DNA-PFs-AlClPc during PDT; the results demonstrated a positive response to photo stimulation within the range of light doses used (300, 600, and 1200mJ/cm2). Reduced viability and increased cell death were observed with increasing doses than in the controls. As expected, the viability was reduced by more than 30% at the highest dose (1200mJ/cm2). Flow cytometry revealed that the main mechanism of cell death induction was apoptosis (early and late apoptosis). These results demonstrate the potential of applying DNA-PFs-AlClPc as a DDS for other active molecules in the treatment of other pathologies. Furthermore, this system allows other drugs to be associated with DNA-PFs, indicating the potential use of this nanostructure in novel ways for the treatment of different neoplasms, such as oral cancer. Additionally, DNA nanostructured films may be used to support cell growth and subsequently as a "curative material" incorporated with an active or photoactive compound that can induce tissue regeneration. Graphical abstract .

Chitosan Nanoparticles as a Potential Drug Delivery System for Photodynamic Therapy of Cancer

Objective: Chitosan nanoparticles (CS-NP) can imbibe water insoluble anticancer agents into its hydrophobic multicores. In the present study, chitosan nanoparticles, a nanoscale drug carrier system is investigated for its potential as a drug delivery system for porphyrin based photodynamic therapy. Methods: Zinc meso tetra phenyl porphyrin (ZnmTPP) encapsulated CS-NP was prepared by ionic gelation method. The synthesized nanoparticles were characterized using dynamic light scattering studies, zeta potential analysis and AFM analysis. Results: Freshly prepared chitosan nanoparticles had an average hydrodynamic diameter of 175 nm and are nearly spherical in shape as per light scattering measurements and atomic force imaging respectively. As nanoscale drug carriers, (ZnmTPP) encapsulated chitosan nanoparticles exhibited high encapsulation efficiency and controlled release pattern. The encapsulated photosensitizer exhibited efficient singlet oxygen generation upon photo irradiation, retaining the photosensitization capacity of encapsulated hydrophobic ZnmTPP. The in vitro phototoxicities of free and nano-encapsulated ZnmTPP, studied using MTT assay in DLA cell lines demonstrate a concentration dependent response of photosensitizer in free and CS-nano formulations.

Evaluation of targeted curcumin (CUR) loaded PLGA nanoparticles for in vitro photodynamic therapy on human glioblastoma cell line.

In this study, antibody-conjugated biodegradable polymeric nanoparticles were developed to enhance the photodaynamic efficiency of curcumin (CUR) on glioblastoma tumor cells. Poly (D, l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) were synthesized and stabilized by polyvinyl alcohol (PVA). Poly(ethylene-alt-maleic anhydride) (PEMA) was used to provide carboxyl groups on the surface of NPs. The CUR or FITC (fluorescein isothiocyanate) was encapsulated in PLGA NPs using the nanoprecipitation method. The carboxylic groups on the surface of the PLGA NPs were covalently conjugated to the amino groups of a monoclonal antibody against EGFRvIII (A-EGFRvIII-f). The prepared NPs were fully characterized by Zetasizer, scanning electron microscope (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR), and then entrapment efficiency (EE), drug loading efficiency (DLE), CUR release, cell internalization, intrinsic cytotoxicity, and phototoxicity were evaluated. Furthermore, the effect of monoclonal antibody (MAb) on the tyrosine phosphorylation of EGFRvIII after photodynamic therapy (PDT) was assessed. The immunoreactivity of the antibody in MAb-PLGA NPs was preserved during the process of conjugation. The selective cellular internalization of MAb-PLGA NPs (FITC or CUR loaded) into the DKMG/EGFRvIII cells (EGFRvIII overexpressed human glioblastoma cell line) in comparison with DK-MGlow (human glioblastoma cell line with low level of EGFRvIII) was also confirmed. MAb-CUR-PLGA NPs were able to show more effective photodynamic toxicity (56% vs. 24%) on the DKMG/EGFRvIII cells compared to CUR-PLGA NPs. These results suggest that the anti-EGFRvIII MAb-CUR-PLGA NPs have potential of targeted drug delivery system for PDT in the overexpressed EGFRvIII tumor cells.

Zeolitic imidazolate metal organic framework-8 as an efficient pH-controlled delivery vehicle for zinc phthalocyanine in photodynamic therapy

To improve the aqueous solubility and cancer targeting of the photosensitizers in photodynamic therapy (PDT), we encapsulated the photosensitizer in a biocompatibility and pH-sensitive drug delivery system, zeolitic imidazolate frameworks-8 (ZIF-8) nanospheres. Powder X-ray diffraction and electron microscopy show that our nanospheres are uniform and single-crystalline particles. Owing to the cleavage of zinc–ligand coordination bonds, more ZnPc–COOH were released much faster in the mild acidic conditions (pH 5.0 and 6.0) in comparison with physiological environment (pH 7.4). By incorporating ZnPc–COOH in ZIF-8, our nanospheres exhibited high singlet oxygen quantum yield and intracellular ROS generation. Cell viability experiments toward HepG2 cells demonstrated the low toxicity of ZIF-8 and the good anticancer efficacy of the nanospheres with low IC50 values (4.2–4.9 μg/mL) under light illumination (670 nm, 1.5 J/cm2). Collectively, these results suggested that our nanospheres are the promising pH-responsive drug delivery systems for PDT.

Synthesis and characterization of doxorubicin modified ZnO/PEG nanomaterials and its photodynamic action

The aim of this study is to investigate a new strategy of combined application of ZnO/PEG nanospheres with anticancer drug of doxorubicin (DOX) in photodynamic therapy (PDT). We were able to fabricate ZnO/PEG nanospheres as the drug carrier of DOX in drug delivery system. The combination of DOX-ZnO/PEG nanocomposites induced the remarkable improvement in the anti-tumor activity, which has been demonstrated by antibacterial activity, drug release and DNA cleavage study. Furthermore, the possible mechanism was explored by optical spectroscopic studies and EPR – spin trapping technique. It was noted that the photodynamic activity of the non-cytotoxic DOX loaded ZnO/PEG nanocomposite could considerably increase cancer cell injury mediated by reactive oxygen species (ROS) under UV irradiation. In our observations demonstrated that ZnO/PEG nanosphere could obviously increase the intracellular concentration of DOX and enhance its potential anti-tumor efficiency, indicating that ZnO/PEG nanosphere could act as an efficient drug delivery carrier importing DOX into target cancer cells. Nearly 91% of loaded drug was released within 26h of incubation of conjugates in vitro in an acidic environment. It suggests that there is an efficient drug release of DOX from DOX-ZnO/PEG nanocomposite. DOX loaded on ZnO/PEG nanomaterials showed antibacterial activity was more pronounced with Gram-positive than Gram-negative bacteria under visible light. DOX-ZnO/PEG nanocomposites were effective against HeLa cell lines under in vitro condition and photocleavage of DNA. This result indicated that ZnO/PEG nanomaterials can be used as a nanocarrier for drug delivery system for PDT.