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.

scholarly journals A Micellar Mitotane Formulation with High Drug Loading and Solubility: Physico-Chemical Characterization and Cytotoxicity Studies in 2D and 3D in Vitro Tumor Models.

2019 ◽  
Author(s):  
Malik Salman Haider ◽  
Jochen Schreiner ◽  
Sabine Kendl ◽  
Matthias Kroiß ◽  
Robert Luxenhofer
Keyword(s):  
Water Solubility ◽  
Drug Loading ◽  
Plasma Concentrations ◽  
Ethanol Solution ◽  
Comparable Efficacy ◽  
Scanning Calorimetry ◽  
High Drug ◽  
Cytotoxicity Studies ◽  
High Drug Loading

Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14-20 mg/L) even after many months of treatment which is caused by low water solubility and unfavorable pharmacokinetic properties such as poor bioavailability and high volume of distribution of MT. The clinical need and previously reported extraordinary high drug loading of poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline)-block-poly(2-methyl-2-oxazoline) (A-pBuOx-A) based micelles for paclitaxel (PTX), led us to develop MT loaded micelles which may enable an injectable formulation. We successfully solubilized up to 6 g/L of MT in an aqueous formulation. The MT loaded nanoformulations were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and powder X-ray<br> <p>diffraction (XRD), confirmed the amorphous nature of drug in the formulations. The polymer itself did not show cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI-H295 both in monolayers and tumor cell spheroids, we demonstrated micellar MT to exhibit comparable efficacy to its ethanol solution. We postulate that this formulation would be suitable for i.v. application and more rapid attainment of therapeutic plasma concentrations. In conclusion, we consider our micellar formulation a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity towards ACC in vitro.</p>

scholarly journals Trisulfide bond–mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity

2020 ◽  
Vol 6 (45) ◽  
pp. eabc1725
Author(s):  
Yinxian Yang ◽  
Bingjun Sun ◽  
Shiyi Zuo ◽  
Ximu Li ◽  
Shuang Zhou ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Self Assembly ◽  
Rational Design ◽  
Colloidal Stability ◽  
Drug Loading ◽  
High Drug ◽  
Tumor Selectivity ◽  
Poor Stability ◽  
High Drug Loading

Rational design of nanoparticulate drug delivery systems (nano-DDS) for efficient cancer therapy is still a challenge, restricted by poor drug loading, poor stability, and poor tumor selectivity. Here, we report that simple insertion of a trisulfide bond can turn doxorubicin homodimeric prodrugs into self-assembled nanoparticles with three benefits: high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity. Compared with disulfide and thioether bonds, the trisulfide bond effectively promotes the self-assembly ability of doxorubicin homodimeric prodrugs, thereby improving the colloidal stability and in vivo fate of prodrug nanoassemblies. The trisulfide bond also shows higher glutathione sensitivity compared to the conventional disulfide bond, and this sensitivity enables efficient tumor-specific drug release. Therefore, trisulfide bond–bridged prodrug nanoassemblies exhibit high selective cytotoxicity on tumor cells compared with normal cells, notably reducing the systemic toxicity of doxorubicin. Our findings provide new insights into the design of advanced redox-sensitive nano-DDS for cancer therapy.

scholarly journals A Micellar Mitotane Formulation with High Drug Loading and Solubility: Physico-Chemical Characterization and Cytotoxicity Studies in 2D and 3D in Vitro Tumor Models.

2019 ◽  
Author(s):  
Malik Salman Haider ◽  
Jochen Schreiner ◽  
Sabine Kendl ◽  
Matthias Kroiß ◽  
Robert Luxenhofer
Keyword(s):  
Water Solubility ◽  
Drug Loading ◽  
Plasma Concentrations ◽  
Ethanol Solution ◽  
Comparable Efficacy ◽  
Scanning Calorimetry ◽  
High Drug ◽  
Cytotoxicity Studies ◽  
High Drug Loading

Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14-20 mg/L) even after many months of treatment which is caused by low water solubility and unfavorable pharmacokinetic properties such as poor bioavailability and high volume of distribution of MT. The clinical need and previously reported extraordinary high drug loading of poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline)-block-poly(2-methyl-2-oxazoline) (A-pBuOx-A) based micelles for paclitaxel (PTX), led us to develop MT loaded micelles which may enable an injectable formulation. We successfully solubilized up to 6 g/L of MT in an aqueous formulation. The MT loaded nanoformulations were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and powder X-ray<br> <p>diffraction (XRD), confirmed the amorphous nature of drug in the formulations. The polymer itself did not show cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI-H295 both in monolayers and tumor cell spheroids, we demonstrated micellar MT to exhibit comparable efficacy to its ethanol solution. We postulate that this formulation would be suitable for i.v. application and more rapid attainment of therapeutic plasma concentrations. In conclusion, we consider our micellar formulation a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity towards ACC in vitro.</p>

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

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.

scholarly journals In-vitro study of formulation and evaluation of nanosuspension of tamoxifen

2018 ◽  
Vol 7 (5) ◽  
pp. 926
Author(s):  
Somasekhar M. Reddy ◽  
Navispaul N. Sriganth ◽  
Chandra S. Kumar ◽  
Santosh C. Gursale ◽  
Vijay V. Ragavan
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Size Distribution ◽  
Drug Loading ◽  
Polarized Light ◽  
Scanning Calorimetry ◽  
High Drug ◽  
Dissolution Properties ◽  
High Drug Loading

Background: Nanosuspension technology has been developed as a promising candidate for efficient delivery of hydrophobic drugs. It could maintain the required crystalline state of the drug with reduced particle size, leading to an increased reporting on dissolution rate and therefore improved bioavailability.Methods: In this paper, we report on the preparation of Tamoxifen nanosuspension by high-pressure homogenization (HPH). The aim is to obtain a stable nanosuspension with an increased drug saturation solubility and dissolution velocity. The morphology and particle size distribution of the modified nanosuspensions were characterized by the means of several analyses that included: transmission electron microscopy (TEM), polarized light microscopy (PLM), scanning electron microscopy, differential scanning calorimetry (DSC) and powder X- ray diffractometry (XRD).Results: HPH was employed to produce aqueous drug nanosuspensions with fine solubility and dissolution properties, which render the produced particles stable up to one month. In addition, the prepared nanosuspensions possessed a high drug-loading efficiency (10%). The recoded zeta potential values (≈ -27 mV) indicated that the prepared nanosuspensions possess a higher degree of long-term stability. TEM data showed narrow size distribution with average size 322.7 nm. Morphologically, as indicated from results, the produced nanosuspensions have a homogenous distribution even after redispersion, indicating the stability of the product.Conclusions: It was possible to obtain Tamoxifen nanosuspensions with fine solubility and dissolution properties. Nanosuspensions possessed a high drug- loading (10%), which could reduce the dosage administration and gastrointestinal side effects. HPH can be employed to produce aqueous drug nanosuspensions that are stable up to one month. Aqueous nanosuspension can be converted to dry nanocrystals by lyophilization which offer superior physicochemical properties.

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

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.

scholarly journals Preparation of high drug-loading celastrol nanosuspensions and their anti-breast cancer activities in vitro and in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiantian Huang ◽  
Yian Wang ◽  
Yiping Shen ◽  
Hui Ao ◽  
Yifei Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Loading ◽  
High Drug ◽  
High Drug Loading

scholarly journals Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy

2020 ◽  
Vol 21 (13) ◽  
pp. 4677 ◽  
Author(s):  
Yihalem Abebe Alemayehu ◽  
Wen-Lu Fan ◽  
Fasih Bintang Ilhami ◽  
Chih-Wei Chiu ◽  
Duu-Jong Lee ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cellular Uptake ◽  
Self Assembly ◽  
Apoptotic Cell ◽  
Drug Loading ◽  
Stimuli Responsive ◽  
High Drug ◽  
High Drug Loading

The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.

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