scholarly journals Soybean lecithin stabilizes disulfiram nanosuspensions with a high drug-loading content: remarkably improved antitumor efficacy

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Haowen Li ◽  
Biao Liu ◽  
Hui Ao ◽  
Jingxin Fu ◽  
Yian Wang ◽  
...  
Keyword(s):  
Soybean Lecithin ◽  
Drug Loading ◽  
Antitumor Efficacy ◽  
Oral Drug ◽  
High Drug ◽  
Breast Cancer Chemotherapy ◽  
Intravenous Injections

AbstractDisulfiram (DSF) has been considered as “Repurposing drug” in cancer therapy in recent years based on its good antitumor efficacy. DSF is traditionally used as an oral drug in the treatment of alcoholism. To overcome its rapid degradation and instability, DSF nanosuspensions (DSF/SPC-NSps) were prepared using soybean lecithin (SPC) as a stabilizer of high drug-loaded content (44.36 ± 1.09%). Comprehensive characterization of the nanosuspensions was performed, and cell cytotoxicity, in vivo antitumor efficacy and biodistribution were studied. DSF/SPC-NSps, having a spherical appearance with particle size of 155 nm, could remain very stable in different physiological media, and sustained release. The in vitro MTT assay indicated that the cytotoxicity of DSF/SPC-NSps was enhanced remarkably compared to free DSF against the 4T1 cell line. The IC50 value decreased by 11-fold (1.23 vs. 13.93 μg/mL, p < 0.01). DSF/SPC-NSps groups administered via intravenous injections exhibited better antitumor efficacy compared to the commercial paclitaxel injection (PTX injection) and had a dose-dependent effect in vivo. Notably, DSF/SPC-NSps exhibited similar antitumor activity following oral administration as PTX administration via injection into a vein. These results suggest that the prepared nanosuspensions can be used as a stable delivery vehicle for disulfiram, which has potential application in breast cancer chemotherapy.

scholarly journals Design, Preparation, and Characterization of Dioscin Nanosuspensions and Evaluation of Their Protective Effect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-Ye JU ◽  
Kun-Xia Hu ◽  
Guo-Wang Zhao ◽  
Zhi-Shu Tang ◽  
Xiao Song
Keyword(s):  
Particle Size ◽  
Protective Effect ◽  
Soybean Lecithin ◽  
Chemical Properties ◽  
Spherical Shape ◽  
Positive Control ◽  
The Body

The purpose of this study was to prepare a dioscin nanosuspension (Dio-NS) that has a better distance and high solubility for oral administration and to evaluate its hepatoprotective effects. Optimal primary manufacture parameters, including shear time, shear speed, emulation temperature, pressure, and cycles of homogenization, were determined by single-factor experiments. The concentrations of dioscin, SDS, and soybean lecithin were optimized using the central composite design-response surface method, and their effects on the mean particle size (MPS) and particle size distribution of Dio-NS were investigated. Characterization of the Dio-NS formulations included examinations of the surface morphology and physical status of dioscin in Dio-NS, the stability of Dio-NS at different temperatures, in vitro solubility, and liver protective effect in vivo. Under optimal conditions, Dio-NS had an MPS of 106.72 nm, polydispersity index of 0.221, and zeta potential of −34.27 mV. Furthermore, the proportion of dioscin in Dio-NS was approximately 21.26%. The observation of particles with a spherical shape and the disappearance of crystalline peaks indicated that the physical and chemical properties of Dio-NS were altered. Furthermore, we observed that the dissolution of Dio-NS was superior to that of a physical mixture and Dio-GZF. Moreover, Dio-NS was demonstrated to have a protective effect against CCl4-induced acute liver damage in mice that was equivalent to that of silymarin (a positive control drug) at the same dose. The good hepatoprotective effect of our Dio-NS preparation can provide a theoretical basis for investigating its absorption mechanisms in the body.

scholarly journals Fabrication and characterization of sterically stabilized liposomes of topotecan

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Dasharath Patel ◽  
Niteshkumar Patel
Keyword(s):  
Drug Delivery ◽  
Sucrose Solution ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Ethanol Injection ◽  
Stealth Liposomes ◽  
Sterically Stabilized Liposomes

Abstract Background Recently, the development of drug delivery which delivers controlled drug release at the tumor sites emerged as an attractive option for enhancing anticancer therapeutics. Next-generation nanotherapeutics must not contain only the nanoscale but should find their way to the solid tumor via active or passive targeting. Surface modification by pegylated lipids is one of the approaches used to made liposomes long-circulating and passively target the tumor. Pegylation of liposomes help them to alter the pharmacokinetics of drug molecule in vivo. The successful journey of such a complex drug delivery system from bench to clinic requires in-depth understanding and characterization. In this research, we fabricated and characterized sterically stabilized liposomes of topotecan which meets the clinical need. Liposomes have been prepared using ethanol injection-solvent evaporation method followed by extrusion for size reduction. Outer medium was replaced with an isotonic sucrose solution using dialysis followed by drug loading. We characterized liposomes’ membrane phase and dynamics, drug and lipid quantification, size distribution, state of encapsulated drug, internal volume and internal pH of liposomes, presence, and thickness of grafted PEG on the liposomes surface, and in vitro leakage test. Results All these studied parameters directly or indirectly provide information regarding the pharmacokinetic behavior of the formulation and the tumor-targeting property of the drugs in vivo. We encapsulated the topotecan in nanoliposomes with pegylation on the surface resulting in long-circulating stealth liposomes. Nanoliposomes remotely loaded with topotecan by transmembrane gradient method. Conclusion Our in vitro characterization of topotecan liposomes provides an explanation for the good therapeutic efficacy of tumor cells.

scholarly journals A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Hai Wang ◽  
Pranay Agarwal ◽  
Shuting Zhao ◽  
Jianhua Yu ◽  
Xiongbin Lu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Encapsulation Efficiency ◽  
Near Infrared ◽  
Drug Loading ◽  
Eukaryotic Cell ◽  
Silica Matrix ◽  
High Drug ◽  
Theranostic Agents

Abstract Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ∼87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

In vitro and in vivo evaluation of sunitinib eluting beads.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 246-246
Author(s):  
Pierre E. Bize ◽  
Olivier Jordan ◽  
Katrin Fuchs ◽  
Olivier Dormond ◽  
Rafael Duran ◽  
...  
Keyword(s):  
Hepatic Artery ◽  
Drug Loading ◽  
Rabbit Model ◽  
Internal Standard ◽  
Embolic Agent ◽  
Liver Malignancies ◽  
In Vivo Evaluation ◽  
High Drug

246 Background: Chemoembolization is used to treat liver malignancies. However recurrence occurs frequently, possibly because of neoangiogenesis triggered by ischemia caused by the embolic agent. In this context, the combination of an embolic agent with an anti-angiogenic drug seems appealing. This study characterizes the in vitro loading and release profile of sunitinib eluting beads of different sizes and their pharmacokinetic profile in a rabbit model. Methods: 70-150 μm and 100-300 μm drug eluting beads (DC Bead, Biocompatibles UK) were loaded by incubation in a sunitinib hydrochloride solution. Drug was quantified by spectrophotometry at 430 nm. Drug release was measured over one-week periods and normalized using an internal standard in 30% ethanol in NaCl 0.9%. New-Zealand white rabbits were used. Eight animals received 0.2 ml of 100-300 μm DC Bead loaded with 6 mg of sunitinib in the hepatic artery (group 1) and 4 animals received 6 mg of sunitinib p.o. (group 2). Half of the animals were sacrificed after 6 hours and half after24 hours. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was determined by tandem mass spectroscopy (LC MS/MS) at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS. Results: High drug loading was obtained for both microsphere bead sizes. Particle shrinking was observed with adsorption of sunitinib. Almost complete release of sunitinib was detected under physiological conditions, with very similar release for 70-150 μm and 100-300 μm (t50%=1.2 h) DC Bead. Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration can be obtained at the site of embolization with minimal systemic passage.

Development of a multifunctional gold nanoplatform for combined chemo-photothermal therapy against oral cancer

Nanomedicine ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. 661-676 ◽  
Author(s):  
Zengying Liu ◽  
Jianbo Shi ◽  
Bangshang Zhu ◽  
Qin Xu
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Photothermal Therapy ◽  
Drug Loading ◽  
Antitumor Efficacy ◽  
Antitumor Effects ◽  
In Vivo Experiments ◽  
Low Toxicity

Aim: To design and fabricate a multifunctional drug-delivery nanoplatform for oral cancer therapy. Materials & methods: Polyethylene glycol-stabilized, PDPN antibody (PDPN Ab)- and doxorubicin (DOX)-conjugated gold nanoparticles (AuNPs) were prepared and evaluated for their cytotoxicity and antitumor efficacy in both chemotherapy and photothermal therapy. Results: The obtained (PDPN Ab)-AuNP-DOX system presents low toxicity, a high drug loading capacity and cellular uptake efficiency. Both in vitro and in vivo experiments demonstrate that (PDPN Ab)-AuNP-DOX has enhanced antitumor efficacy. Treatment with (PDPN Ab)-AuNP-DOX combined with laser irradiation exhibits superior antitumor effects. Conclusion: This (PDPN Ab)-AuNP-DOX system may be used as a versatile drug-delivery nanoplatform for targeted and combined chemo-photothermal therapy against oral cancer.

FORMULATION AND EVALUATION OF MICROSPHERES FOR NASAL DELIVERY OF ANTI-HYPERTENSIVE DRUG

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (10) ◽  
pp. 21-26
Author(s):  
S. S Shelake ◽  
◽  
R. M Mhetre ◽  
S. V Patil ◽  
S. S Patil ◽  
...  
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Nasal Delivery ◽  
In Vivo Studies ◽  
Oral Drug ◽  
Hypertensive Drug

Lisinopril is used in the treatment of hypertension and heart failure in myocardial infarction and also in diabetic nephropathy. It is very poorly absorbed from GIT. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The microspheres prepared by emulsion solvent evaporation method were characterized for encapsulation efficiency, drug loading, particle size, surface morphology, degree of swelling, ex vivo mucoadhesion, drug release and ex vivo diffusion studies. Entrapment efficiency of microspheres was in range of 84.95±0.50% to 97.44±0.61% mucoadhesion was 83.76% and 94.41% and drug release up to 40 minutes was 53.66% to 88.32%. In ex vivo studies, the microspheres showed good bioavailability by nasal route compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres are better than single carbopol-based formulation for the delivery of lisinopril.

scholarly journals A novel preparative method for nanoparticle albumin-bound paclitaxel with high drug loading and its evaluation both in vitro and in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250670
Author(s):  
Yue Gao ◽  
Jingxue Nai ◽  
Zhenbo Yang ◽  
Jinbang Zhang ◽  
Siyu Ma ◽  
...  
Keyword(s):  
Self Assembly ◽  
Drug Loading ◽  
Preparative Method ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Spectra Analysis ◽  
High Drug ◽  
High Drug Loading

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value.

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