Loading Efficiency Of Cisplatin Research Articles

Synergistic Combination Chemotherapy of Lung Cancer: Cisplatin and Doxorubicin Conjugated Prodrug Loaded, Glutathione and pH Sensitive Nanocarriers.

PurposeProdrug technology-based combination drug therapy has been exploited as a promising treatment strategy to achieve synergistic lung cancer therapy, reduce drug dose, and decrease side effects. In the present study, we synthesized a pH and glutathione (GSH) sensitive prodrug, cisplatin (CIS) and doxorubicin (DOX) conjugates (CIS-DOXp). CIS-DOXp was loaded by nanocarriers and delivered into the tumor site.MethodspH and GSH sensitive CIS-DOX prodrug (CIS-DOXp) was synthesized by conjugating GSH responsive CIS prodrug with pH sensitive DOX prodrug. CIS-DOXp-loaded nanocarriers (CIS-DOXp NC) were prepared using emulsification and solvent evaporation method. The morphology, particle size, polydispersity index (PDI) and zeta potential of nanocarriers were measured. In vitro cytotoxicity of nanocarriers and the corresponding free drugs was examined using the MTT assay. In vivo anti-tumor efficiency and biodistribution behaviors were evaluated on lung cancer mice models.ResultsThe size, PDI, zeta potential, CIS loading efficiency, and DOX loading efficiency of CIS-DOXp NC were 128.6 ± 3.2 nm, 0.196 ± 0.021, 15.7 ± 1.7 mV, 92.1 ± 2.1%, and 90.4 ± 1.8%, respectively. The best cell killing ability (the lowest combination index of 0.57) was found at the combination ratio of 1:3 (CIS:DOX, w/w) in the drugs co-loaded formulations, indicating the strongest synergism effect. CIS-DOXp NC showed the best tumor inhibition efficiency (79.9%) in mice with negligible body weight lost.ConclusionCIS-DOXp NC could be applied as a promising system for the synergistic chemotherapy of lung cancer.

Synthesis of chitosan-grafted-poly(N-vinylcaprolactam) coated on the thiolated gold nanoparticles surface for controlled release of cisplatin

The gold nanoparticles surface was modified by thioglycolic acid ligand and their surface was coated by the chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) copolymer. The cisplatin anticancer drug was loaded into the synthesized nanocarriers and its performance was investigated for the treatment of MCF-7 breast cancer cells in vitro. The synthesized nanoparticles were characterized using FTIR, DLS, TEM, SEM, EDX and TGA analysis. The lower critical solution temperature (LCST) of PNVCL/chitosan and PNVCL/chitosan coated gold nanoparticles were found to be 38 and 39 °C, respectively. The cisplatin loading efficiency, cisplatin release from nanoparticles at different temperatures and pH values as well as the pharmacokinetic studies were examined. The maximum cisplatin release from nanoparticles was achieved at T > LCST (42 °C) and pH of 5. The Korsemeyer-Peppas model was best described the cisplatin release from nanoparticles. The maximum MCF cell death was found to be 92% using cisplatin loaded-gold/TGA/chitosan-g-PNVCL nanoparticles under an induction heating system.

Fabrication and Cytotoxicity of Fucoidan-Cisplatin Nanoparticles for Macrophage and Tumor Cells.

Fucoidan, an anionic, sulfated polysaccharide from brown seaweed, is known to exhibit antitumor and immunomodulatory functions. To develop an immune protection and chemotherapeutic agent, fucoidan-cisplatin nanoparticles (FCNPs) were designed. FCNPs were prepared by mixing cisplatin with fucoidan solution or fucoidan with cisplatin solution, followed by dialysis to remove trace elements. The nanoparticles, comprising 10 mg of fucoidan and 2 mg of cisplatin, which exhibited the highest cisplatin content and loading efficiency during the production process, were named as Fu100Cis20. The cisplatin content, cisplatin loading efficiency, nanoparticle size, and zeta potential of Fu100Cis20 were 18.9% ± 2.7%, 93.3% ± 7.8%, 181.2 ± 21.0 nm, and −67.4 ± 2.3 mV, respectively. Immune protection assay revealed that Fu100Cis20-treated RAW264.7 cells were protected from the cytotoxicity of cisplatin. Furthermore, antitumor assay indicated that Fu100Cis20-treated HCT-8 cells showed stronger cytotoxicity than those treated with cisplatin alone. These results suggested that fucoidan-based nanoparticles exhibited suitable particle size and high drug encapsulation, and that Fu100Cis20 has potential application in both immunotherapy and chemotherapy.

Efficient Loading of cisplatin into Superabsorbent Polymer Microsphere in the treatment of hepatocellular carcinoma.

Background: Although Superabsorbent Polymer (SAP) microsphere has been useful in treatment of multiple and large hepatocellular carcinoma, efficient loading procedure of cisplatin onto SAP was not established. Loading efficiency of cisplatin was evaluated from the viewpoint of passive concentration gradient and ionic strength. Methods: To load cisplatin into SAP particle, 50mg of cisplatin powder was dissolved in three manners of aqueous solutions: (a) 50mg of cisplatin powder plus 35ml of warmed physiological saline solution (0.9%), (b) 5ml of physiological saline solution (0.9%) plus a half of solution (5ml) of the product made from 50mg of cisplatin powder in 10ml of iohexol 350mgI/ml, and (c) 10ml of iohexol 350mgI/ml plus 0.25ml of 10% NaCl solution Results: Cisplatin dissolved sufficiently in all the three methods. Average amounts of loaded cisplatin into SAP particles were 1.7mg in solution (a), 6.6mg in solution (b), and 11.8mg in solution (c). Since alteration of ionic strength in the method (c) significantly affect the extent of SAP swelling, addition of 0.25ml of 10% NaCl was unquestionably necessary. Release of cisplatin from SAP was evidently gradual, showing 83.1% after 6 hours in static elution experiment and 68.6% after 1 hour in dynamic elution experiment. Conclusions: Cisplatin-loaded SAP may act as a drug delivery system for treatment of liver cancer, and loading of cisplatin should be consciously performed considering cisplatin concentration and ionic strength. (225words)

Efficacy comparison of nanoniosomal and pegylated nanoniosomal Cisplatin on A172 cell line

In this study, Cisplatin was loaded into nanoniosom and pegylated nanoniosom employing reverse phase evaporation method. Span 60, cholesterol and Cisplatin were combined together at certain concentrations in this method. This study reports the efficacy of nanoniosome Cisplatin and pegylated nanoniosome Cisplatin on brain cancer (A172) cell line. All of the results are presented from three independent tests. The obtained results showed that the stability of prepared formulation was increased by pegylation. Encapsulation efficiency and loading efficiency of Cisplatin in pegylated and non-pegylated niosomal formulations were estimated 48.2±2.05%, 43.6±4.59%, 4.38±0.28%, 4.36±0.08%, respectively. The average diameters of pegylated and non-pegylated nanoparticles of niosomes were determined by Zeta sizer which was 205.5±4.60 nm and 242.1±5.10 nm, respectively. The release of drug was studied by dialysis method. The amounts of drug released from pegylated and non-pegylated nanoniosomes were calculated 82.73±1.36% and 97.53±0.55% during 48 hr, respectively. The toxicity of formulated Cisplatin was studied by MTT assay and the results revealed that the cytotoxicity effect of pegylated nanoniosomal Cisplatin was more than nanoniosomal Cisplatin. The IC50 for nanoniosomal Cisplatin was estimated 123.2±0.98 μg/mL while IC50 for pegylated nanoniosomal formulation was calculated 79.8±1.14 μg/mL.

Kinetics of Cisplatin Release by In-Vitro Using Poly(D,L-Lactide) Coated ${\rm Fe}_{3}{\rm O}_{4}$ Nanocarriers

Applications of nanoparticles as drug delivery systems for anticancer therapeutics have great potential to revolutionize the future of cancer therapy. In the present study, Fe3O4 nanoparticles were synthesized by co-precipitation method in the alkaline pH medium. The synthesized nanoparticles were characterized by X-ray diffraction and high resolution scanning electron microscope techniques. These analyses reveal the formation of agglomerated single phase Fe3O4 nanoparticles with average crystallite size of 8 nm. The emulsification solvent evaporation method was employed to prepare anti-cancer drug cisplatin loaded biodegradable poly (D, L-lactide) coated magnetic carriers. Fourier transform infrared spectroscopy shows the presence of cisplatin loaded poly(D,L-lactide) coating on the surface of Fe3O4 nanoparticles. Cisplatin loading efficiency and kinetics of drug release in-vitro were investigated by UV-Vis spectrophotometer. The loading efficiency of the drug was found to be 80% and from that 53% of the drug was released over a period of 70 h in phosphate buffer saline (pH 7.4) at ~ 37°C.

Controlling the morphology and surface property of magnetic/cisplatin-loaded nanocapsules via W/O/W double emulsion method

Here, a well-controlled method to prepare magnetic/cisplatin-loaded nanocapsules with different morphologies has been developed by using a W/O/W double emulsion-solvent evaporation technique. This study focuses on the influences of solvent removal method and existence of stabilizers on the characteristics of nanocapsules in a double emulsion procedure. Biodegradable poly(lactic-co-glycolic acid) [PLGA] nanocapsules were used for encapsulation of cisplatin and magnetic nanoparticles. The effect of preparation conditions on the size, morphology and surface properties of PLGA nanocapsules containing cisplatin and magnetic nanoparticle were investigated too. Solvent removal from the double emulsion was carried out by using two methods; slow evaporation at ambient condition and fast evaporation under reduced pressure. PLGA nanocapsules were prepared in the presence of stabilizers during the first and second emulsification steps and also without any stabilizer. Changing in the morphology and decrease in mean diameter of magnetic nanocapsules were observed when slow evaporation was exploited in comparison with evaporation at reduced pressure. It was found that the loading efficiency of cisplatin was dramatically dependent on the solvent removal method. This step had a significant effect on morphology and size. DLS data showed that the mean diameter of magnetic nanocapsules was ranging between 142 and 384nm with polydispersity index of 0.071–0.111 with zeta potential from −10.5 to−16.5mV. On the other hand, the loading efficiency of cisplatin was related to the preparation conditions and was between 41 and 62% (w/w). The prepared nanocapsules were characterized by SEM and AFM to observe surface topography. These micrographs reveal a spherical shape of magnetic nanocapsules with smooth surface and almost no aggregation was observed. TEM analysis was used to investigate the internal morphology of magnetic/cisplatin-loaded nanocapsules, too.

Cisplatin‐incorporated hyaluronic acid nanoparticles based on ion‐complex formation

The aim of this study is to prepare cisplatin-incorporated nanoparticles based on ion complex formation between hyaluronic acid (HA) and cisplatin for antitumor drug delivery. To prepare nanoparticles using HA, bulk HA was degraded by hyaluronidases (HAses). Cisplatin-incorporated HA nanoparticles were prepared by mixing cisplatin with an aqueous solution of HA and then the nanoparticle solution was dialyzed to remove trace elements. Since glioma tumor cell lines are able to secrete HAse, extracts from U343MG and U87MG cell lines were used to test the release of cisplatin from the nanoparticles. The morphological observation of the cisplatin-incorporated nanoparticles showed that they had spherical shapes with a particle size around 100-200 nm. The loading efficiency of cisplatin in the nanoparticles was about 67-81% (w/w) and cisplatin was continuously released from the nanoparticles for 4 days. Especially, the release rate of cisplatin from the nanoparticles increased when HAse was added to the release medium. In the results of the HA zymography, the U343MG cell line secreted HAse, while the U87MG cell line did not. When the extracts from U343MG were added to the release medium, the release rate of cisplatin was slightly increased, while the extracts from U87MG did not significantly affect the release rate of cisplatin. In conclusion, cisplatin-incorporated nanoparticles have sufficiently small particle sizes to use as a drug targeting system. The release of cisplatin from the nanoparticles was responsive to the secretion of HAse. These nanoparticles are suitable vehicles for an antitumor drug targeting system.