Niosomal Form Research Articles

Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy

BackgroundThe systemic administration of cytotoxic chemotherapeutic agents for cancer treatment often has toxic side effects, limiting the usage dose. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. This study investigated the augmentation of therapeutic effectiveness with the co-administration of paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and curcumin (CUR; a chemosensitizer) in an MCF-7 cell line.ResultsWe optimized niosome formulations in terms of surfactant and cholesterol content. Afterward, the novel cationic PEGylated niosomal formulations containing Tween-60: cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to serve as a model for better transfection efficiency and improved stability. The optimum formulations represented potential advantages, including extremely high entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth-surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both CUR and PTX), sustained release, small diameter (~ 90 nm for both agents), desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX kinetic release could be adequately fitted to the Higuchi model. A threefold and 3.6-fold reduction in CUR and PTX concentration was measured, respectively, when the CUR and PTX was administered in nano-niosome compared to free CUR and free PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the combination treatment of CUR and PTX was particularly effective in enhancing the cytotoxicity activity against MCF-7 cells.ConclusionsMost importantly, CUR and PTX, in both free form and niosomal forms, were determined to be less toxic on MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate that the combination therapy of PTX with CUR using the novel cationic PEGylated niosome delivery is a promising strategy for more effective breast cancer treatment.

Свойства разработанной ниосомальной формы противоопухолевого вещества N-hydroxy-2-(2-(naphthalen-2-yl)-1H-Indol-3-yl)-2-phenylacetamide для лечения глиобластомы

Свойства разработанной ниосомальной формы противоопухолевого вещества N-hydroxy-2-(2-(naphthalen-2-yl)-1H-Indol-3-yl)-2-phenylacetamide для лечения глиобластомы

COMPARATIVE STUDY OF PHARMACOKINETICS OF OFLOXACIN IN A FREE AND NIOSOMAL FORMS IN EXPERIMENTS ON WHITE MICE WHEN ADMINISTERED Per Os

Aim: to study features of pharmacokinetics of ofloxacin as a part of anion PEGylated niosomes on a basis of sorbitan monostearate (Span 60) to experimental white mice per os. Materials and methods: ofloxacin was entrapped in niosomes consisting of Span 60, cholesterol, PEG 4000 and dicetylphosphate. Sizes of niosomes estimated by means of probe microscopy. Efficiency of inclusion of an antibiotic in niosomes defined after removal of free drug by a centrifugation. The analysis of the quantitative contents of ofloxacin in samples carried out a method of a high performance liquid chromatography. Results: we studied the main pharmacokinetic parameters of ofloxacin when used free and niosomal forms of antibiotic to experimental white mice per os. It is shown that use of oral niosomal forms leads to decrease of maximal concentration in serum and increase of ofloxacin half-life by 7,4 times in average compared to the free form. It is determined that bioavailability of ofloxacin in the niosomal form is 154% relative to the free form of the antibiotic. Conclusions: niosomal microcontainers are perspective technology of encapsulation and the directed transport of antibacterial preparations through biological barriers. Using of niosomal formulation of ofloxacin is able to afford to increase considerably efficiency of treatment in comparison with a free form and significantly decrease negative effects of antibiotic therapy.

Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system

Lactic acidosis is a serious, metabolic complication that may occur due to metformin hydrochloride (MH) accumulation during the treatment of diabetes mellitus. The aim of this study is to enhance the bioavailability of MH by oral route. Span 40 and cholesterol were used for the preparation of MH-loaded niosomes by the reverse phase evaporation technique. Dicetyl phosphate (DCP) and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) were used to obtain negatively and positively charged vesicles, respectively. The mean particle size ranged from 223.5 to 384.6 nm and the MH-loaded niosomes’ surface was negatively charged in the absence of charge inducing agents (−16.6 ± 1.4 mV) and also with DCP (−26.9 ± 1.0 mV), while it was positively charged (+8.7 ± 1.2 mV) with DOTAP. High entrapment efficiency was observed in all the formulations. MH-loaded niosomes were found to effectively sustain the release of drug, particularly with positively charged niosomes. The bioavailability of MH-loaded niosomes was assessed by measuring the serum values of glucose and metformin in the different studied Wistar rats groups. The pharmacokinetic data of MH-loaded niosomal preparation showed a significant prolongation and increased intensity of hypoglycemic effect more than that observed for free MH solution. Area above the blood glucose levels–time curve (AAC), maximum hypoglycemic response and time of maximum response (Tmax) were significantly higher (p < 0.001) when MH was administered in niosomal form compared to free drug solution. It could be concluded that MH-loaded niosome is promising extended-release preparation with better hypoglycemic efficiency.

Non-ionic surfactant vesicles, niosomes, as a delivery system for the anti-leishmanial drug, sodium stibogluconate.

Liver and serum concentrations of antimony in the mouse have been determined after administration of sodium stibogluconate in the free, liposomal and niosomal form. High liver and low serum values were attained by the use of both vesicular formulations. Niosomal sodium stibogluconate was shown to be more active than free drug against experimental murine visceral leishmaniasis, an effect apparently dependent on maintaining high drug levels in the infected reticuloendothelial system.

Evaluation of the in-vivo activity and toxicity of amarogentin, an antileishmanial agent, in both liposomal and niosomal forms.

The antileishmanial property of amarogentin, a secoiridoid glycoside isolated from the Indian medicinal plant Swertia chirata, was examined in a hamster model of experimental leishmaniasis. The therapeutic efficacy of amarogentin was evaluated in free and two different vesicular forms, liposomes and niosomes. The amarogentin in both liposomal and niosomal forms was found to be a more active leishmanicidal agent than the free amarogentin; and the niosomal form was found to be more efficacious than the liposomal form at the same membrane microviscosity level. Toxicity studies involving blood pathology, histological staining of tissues and specific enzyme levels related to normal liver function showed no toxicity. Hence, amarogentin incorporated in liposomes or niosomes may have clinical application in the treatment of leishmaniasis.

The effect of monomers and of micellar and vesicular forms of non-ionic surfactants (Solulan C24 and Solulan 16) on Caco-2 cell monolayers.

Measurements of transepithelial electrical resistance (TEER), the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) test and monitoring of poly(ethylene glycol) (PEG) transport have been used to study the effects of the non-ionic surfactants Solulan C24 and Solulan 16, either free in solution or as an integral part of niosome bi-layers, on intestinal epithelial cells from man (Caco-2 cell monolayers). The effects on epithelial integrity and on the transport of the hydrophilic drug metformin depend on the concentration of the surfactants. At concentrations above 1% the effect on TEER of the surfactant in niosomal form and free in solution were equivalent whereas cell viability was preserved to a higher concentration of Solulans when the Solulans were present in the niosomal form. It was concluded that the toxic effect of niosomes arises from free surfactant present in the niosome suspension.

Antitumour activity and pharmacokinetics of niosome encapsulated adriamycin in monolayer, spheroid and xenograft.

Niosomes are multilamellar vesicles formed from nonionic surfactants of the alkyl or dialkyl polyglycerol ether class and cholesterol. Adriamycin has been trapped within vesicles prepared from a monoalkyl triglycerol ether and its activity compared with adriamycin solution in human lung tumour cells grown in monolayer and spheroid culture and in tumour xenografted nude mice. The activity of the encapsulated adriamycin in vitro is maintained with similar clonogenic survival curves following treatment of monolayers and identical growth delays following spheroid exposure. The pharmacokinetics of adriamycin are altered in vivo in human lung tumour-bearing nude mice, when it is administered in niosomal form. There is prolonged release of drug from the plasma compartment with significantly lower peak levels; lower peak cardiac adriamycin concentrations with a shorter tissue half-life and decreased cardiac AUC and a greater degree of hepatic metabolism to inactive 7-deoxyaglycones. The tumour peak drug level and AUC was similar irrespective of the mode of administration of adriamycin. The growth delay (i.e. the time taken for the tumour volume to double) was significantly longer for adriamycin (15 days) and niosomal adriamycin (11 days) than for control (5.8 days). It is possible that the therapeutic ratio of adriamycin could be enhanced by administration in niosomal form.