Dual-responsive mPEG-PLGA-PGlu hybrid-core nanoparticles with a high drug loading to reverse the multidrug resistance of breast cancer: An in vitro and in vivo evaluation

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.

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

PLoS ONE ◽

10.1371/journal.pone.0250670 ◽

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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Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

10.21203/rs.2.19811/v2 ◽

2020 ◽

Author(s):

Wenjun Jiang ◽

Jiyuan Chen ◽

Chunai Gong ◽

Yuanyuan Wang ◽

Yuan Gao ◽

...

Keyword(s):

Prostate Cancer ◽

Graphene Oxide ◽

Drug Loading ◽

Electron Interaction ◽

Castration Resistant Prostate Cancer ◽

High Drug ◽

Castration Resistant ◽

High Drug Loading

Abstract Background: Enzalutamide (Enz) has shown limited bioavailability via oral administration. It is easy for patients to develop into castration-resistant prostate cancer (CRPC) due to resistance to 18-24 months of androgen deprivation therapy (ADT). Moreover, it is hard to delivery Enz in vivo for low drug loading (DL) and encapsulation efficiency (EE).Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for castration-resistant prostate cancer (CRPC) intravenous treatment, with high drug loading efficiency.Methods: Aminated graphene quantum dots (GQDs) were first cross-linked via disulfide bonds into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.Results: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could promote the inhibition of cell growth in vitro against CRPC cells. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo. Conclusions: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC.

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Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

10.21203/rs.2.19811/v1 ◽

2019 ◽

Author(s):

Wenjun Jiang ◽

Jiyuan Chen ◽

Chunai Gong ◽

Yuanyuan Wang ◽

Yuan Gao ◽

...

Keyword(s):

Prostate Cancer ◽

Graphene Oxide ◽

Drug Loading ◽

Castration Resistant Prostate Cancer ◽

High Drug ◽

Castration Resistant ◽

Drug Loading Efficiency ◽

High Drug Loading

Abstract Background: Enzalutamide (Enz) has shown limited bioavailability via oral administration and is easy for patients to develop into castration-resistant prostate cancer (CRPC) due to resistance to 18-24 months of androgen deprivation therapy (ADT). Moreover, it is hard to delivery Enz for low drug loading (DL) and encapsulation efficiency (EE). Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for castration-resistant prostate cancer (CRPC) intravenous treatment, with high drug loading efficiency and good biocompatibility.Methods: Aminated graphene quantum dots (GQDs) were first cross-linked via a disulfide bond into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.Results: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could promote the inhibition of cell growth in vitro against CRPC cells, while TP-GQDss alone did not show any obvious cytotoxicity on CRPC cells after 24 h of incubation. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo. Conclusions: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as a intravenous therapy platform for CRPC.

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Preparation and In Vivo Evaluation of Dichloro(1,2-Diaminocyclohexane)platinum(II)-Loaded Core Cross-Linked Polymer Micelles

Chemotherapy Research and Practice ◽

10.1155/2012/905796 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Hardeep S. Oberoi ◽

Natalia V. Nukolova ◽

Yi Zhao ◽

Samuel M. Cohen ◽

Alexander V. Kabanov ◽

...

Keyword(s):

Drug Loading ◽

Xenograft Model ◽

Tumor Xenograft ◽

Ovarian Cancer Cells ◽

In Vivo Evaluation ◽

Block Copolymer Micelles ◽

Copolymer Micelles ◽

High Drug Loading

The therapeutic performance of oxaliplatin can be improved by incorporating the central cis-dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) motif into the core cross-linked block copolymer micelles. We describe here the preparation, cellular uptake, and in vivo evaluation of core cross-linked micelles loaded with DACHPt. Stable drug-loaded micelles were prepared at high drug loading (~25 w/w%) and displayed a considerably increased in vitro cytotoxicity compared to free oxaliplatin against A2780 ovarian cancer cells. The DACHPt-loaded micelle formulation was well tolerated in mice and exhibited improved antitumor activity than oxaliplatin alone in an ovarian tumor xenograft model.

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Design of dual-responsive nanocarries with high drug loading capacity based on hollow mesoporous organosilica nanoparticles

Materials Chemistry and Physics ◽

10.1016/j.matchemphys.2019.05.025 ◽

2019 ◽

Vol 233 ◽

pp. 230-235 ◽

Cited By ~ 4

Author(s):

Li-li Lu ◽

Wen-ya Xiong ◽

Jun-bin Ma ◽

Tian-fang Gao ◽

Si-yuan Peng ◽

...

Keyword(s):

Drug Loading ◽

Loading Capacity ◽

High Drug ◽

Dual Responsive ◽

Mesoporous Organosilica ◽

High Drug Loading

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Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽

10.3390/pharmaceutics13081210 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1210

Author(s):

Xieguo Yan ◽

Shiqiang Wang ◽

Kaoxiang Sun

Keyword(s):

Drug Loading ◽

Entrapment Efficiency ◽

In Vitro Dissolution ◽

Dissolution Behavior ◽

In Vivo Evaluation ◽

Long Term Treatment ◽

Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

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