F. Baris Barlas

Controlled release of anticancer drug Paclitaxel using nano-structured amphiphilic star-hyperbranched block copolymers

In the present study, two amphiphilic star-hyperbranched copolymers based on poly(methyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PMMA-b-PHEMA), with different hydrophilic PHEMA segment contents (PMMA-b-PHEMA-1, and PMMA-b-PHEMA-2), were synthesized, and their drug loading and release profiles were examined using Paclitaxel (PTX) as a model drug. The drug loading capacities and encapsulation efficiencies were found to be similar in both polymers. The encapsulation efficiencies were found to be prominent at 98% and 98.5% for PMMA-b-PHEMA-1 and PMMA-b-PHEMA-2, respectively. On the other hand, the drug release behaviors varied in favor of the block copolymer comprising shorter PHEMA chains (PMMA-b-PHEMA-1). Additionally, to assess the biological effects of PTX-loaded polymers, human non-small cell lung carcinoma (A549) cells were used. Cell viability and cell cycle analysis showed that both polymers were non-toxic to cells. The cytotoxic effect of PTX-loaded PMMA-b-PHEMA-1 on A 549 cells was greater (66.49% cell viability at 5.0 ng mL−1 PTX) than that of PMMA-b-PHEMA-2 (72.47% cell viability at 5.0 ng mL−1 PTX), consistent with the drug release experiments.

Bio-active nanoemulsions enriched with gold nanoparticle, marigold extracts and lipoic acid: In vitro investigations.

A novel and efficient approach for the preparation of enriched herbal formulations was described and their potential applications including wound healing and antioxidant activity (cell based and cell free) were investigated via in vitro cell culture studies. Nigella sativa oil was enriched with Calendula officinalis extract and lipoic acid capped gold nanoparticles (AuNP-LA) using nanoemulsion systems. The combination of these bio-active compounds was used to design oil in water (O/W) and water in oil (W/O) emulsions. The resulted emulsions were characterized by particle size measurements. The phenolic content of each nanoemulsion was examined by using both colorimetric assay and chromatographic analyses. Two different methods containing cell free chemical assay (1-diphenyl-2-picrylhydrazyl method) and cell based antioxidant activity test were used to evaluate the antioxidant capacities. In order to investigate the bio-activities of the herbal formulations, in vitro cell culture experiments, including cytotoxicity, scratch assay, antioxidant activity and cell proliferation were carried out using Vero cell line as a model cell line. Furthermore, to monitor localization of the nanoemulsions after application of the cell culture, the cell images were monitored via fluorescence microscope after FITC labeling. All data confirmed that the enriched N. sativa formulations exhibited better antioxidant and wound healing activity than N. sativa emulsion without any enrichment. In conclusion, the incorporation of AuNP-LA and C. officinalis extract into the N. sativa emulsions significantly increased the bio-activities. The present work may support further studies about using the other bio-active agents for the enrichment of herbal preparations to strengthen their activities.

Combining anti-cancer drugs with artificial sweeteners: synthesis and anti-cancer activity of saccharinate (sac) and thiosaccharinate (tsac) complexes cis-[Pt(sac)2(NH3)2] and cis-[Pt(tsac)2(NH3)2].

The new platinum(II) complexes cis-[Pt(sac)2(NH3)2] (sac=saccharinate) and cis-[Pt(tsac)2(NH3)2] (tsac=thiosaccharinate) have been prepared, the X-ray crystal structure of cis-[Pt(sac)2(NH3)2] x H2O reveals that both saccharinate anions are N-bound in a cis-arrangement being inequivalent in both the solid-state and in solution at room temperature. Preliminary anti-cancer activity has been assessed against A549 human alveolar type-II like cell lines with the thiosaccharinate complex showing good activity.

Complex Structured Fluorescent Polythiophene Graft Copolymer as a Versatile Tool for Imaging, Targeted Delivery of Paclitaxel, and Radiotherapy.

Advances in polymer chemistry resulted in substantial interest to utilize their diverse intrinsic advantages for biomedical research. Especially, studies on drug delivery for tumors have increased to a great extent. In this study, a novel fluorescent graft copolymer has been modified by a drug and targeting moiety and the resulting structure has been characterized by alterations in fluorescent intensity. The polythiophene based hybrid graft copolymer was synthesized by successive organic reactions and combination of in situ N-carboxy anhydride (NCA) ring opening and Suzuki coupling polymerization processes. Initially, targeted delivery of the graft copolymer was investigated by introducing a tumor specific ligand, anti-HER2/neu antibody, on the structure. The functionalized polymer was able to differentially indicate HER2-expressing A549 human lung carcinoma cells, whereas no signal was obtained for Vero, monkey kidney epithelial cells, and HeLa, human cervix adenocarcinoma cells. After integrating paclitaxel into the structure, cell viability, cell cycle progression, and radiosensitivity studies demonstrate HER2/neu targeting polymers were most effective to inhibit cell proliferation. Importantly, the graft copolymer used had no cytotoxic effects to cells, as evidenced by cell viability and cell cycle analysis. This work clearly confirms that a specially designed and fabricated graft copolymer with a highly complex structure is a promising theranostic agent capable of targeting tumor cells for diagnostic and therapeutic purposes.

Multimodal theranostic assemblies: double encapsulation of protoporphyrine-IX/Gd3+ in niosomes

Theranostic therapy is one of the most promising methods in cancer research, which simultaneously allows the treating and real-time monitoring of cancer. In the present study, a new method was developed to achieve advanced theranostic therapy by double encapsulation of gadolinium nanoparticles (GdNP) and protoporphyrin IX (PpIX) into niosomes. Hereby, niosomes are used for encapsulation of GdNP and PpIX, which will be called ‘Gd-PpIX-NI’. Niosomes are chosen as the encapsulation material owing to their high biocompatibility, physical and chemical stability, and fair price. On the other hand, GdNP and PpIX are good sensitizers for radiotherapy (RT) and, particularly, porphyrin structures are one of the most studied agents for photodynamic therapy (PDT). In this study, a multimodal treatment was performed with the combination of PDT and RT by using human alveolar type-II (ATII)-like cells (A549) and human cervical cancer cell line (HeLa). Moreover, ‘Gd-PpIX-NI’ serves as a dual cell imaging probe that provides both fluorescence and magnetic resonance imaging. Characterization of the sizes and zeta potential of the niosomal vesicles was carried out by dynamic light scattering and atomic force microscopy. To determine the cell viability after treatment with Gd-PpIX-NI, followed by PDT and RT application, the MTT method was used. The results showed that Gd-PpIX-NI assembling was homogeneous and consistent in terms of particle size, which is less than 100 nm. This material has potential as a good candidate for both PDT and RT, as well as diagnosis.

Functional poly(p-phenylene)s as targeting and drug carrier materials

ABSTRACT Polymers have a substantial attention in drug delivery systems owing to the diverse intrinsic advantages. It is important to carry the drug to the target site and release to exert its effects. Herein, poly(p-phenylene)s with amino and poly(ethylene glycol) substituents (PPP-NH2-g-PEG) were used as a carrier for doxorubicin (DOX), an anticancer drug, and haloperidol, a sigma receptor targeting ligand. Both human cervix adenocarcinoma cell line (HeLa) and human keratinocyte cell line (HaCaT) having different Sigma receptor 1 (SigmaR1) expression levels were compared. HeLa was found to express twofold SigmaR1 compared to HaCaT cells. Cell imaging studies showed that, DOX cell uptake was higher in HeLa cells when targeted with haloperidol. GRAPHICAL ABSTRACT

Radioiodinated Magnetic Nanoparticles Conjugated With Moxifloxacin: Synthesis and In Vitro Biological Affinities

Magnetic nanoparticles (MNPs) were synthesized and coated with tetraethyl orthosilicate and aminosilane to create functional amino groups. Moxifloxacin (MXF) was conjugated to the modified MNPs using glutaraldehyde as crosslinker. Finally, MXF conjugated magnetic nanoparticles were radiolabeled and their biological affinities such as cell incorporation ratio, cytotoxicity, and their potential as cell imaging probe were investigated using A-549 cells. GRAPHICAL ABSTRACT

Phyto-Niosomes: In Vitro Assessment of the Novel Nanovesicles Containing Marigold Extract

Herbal compounds, so-called phytoconstituents, illustrate poor absorption by living cells. Phytosomes are advanced form of herbal compounds that show higher absorption rate and bioavailability, which results better than conventional plant extracts. Niosomes, which are made of nonionic surfactants, create better chemical and stability conditions besides lipid vesicles. This study covers the preparation, characterization and cell culture applications of phyto-niosomes of Marigold extract. Before the encapsulation process, extracts of selected plants were prepared and the extract that presents best bioactivity was chosen. The resulting phyto-niosomes were characterized and their biological activities including cytotoxicity, wound healing and antioxidant activity were investigated. GRAPHICAL ABSTRACT