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

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.

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

10.26434/chemrxiv.8055773 ◽

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 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.

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

10.26434/chemrxiv.8055773.v1 ◽

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

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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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Optimization and characterization of poly(lactic-co-glycolic acid) nanoparticles loaded with astaxanthin and evaluation of anti-photodamage effect in vitro

Royal Society Open Science ◽

10.1098/rsos.191184 ◽

2019 ◽

Vol 6 (10) ◽

pp. 191184 ◽

Cited By ~ 5

Author(s):

Fangbin Hu ◽

Weikang Liu ◽

Liuliu Yan ◽

Fanhui Kong ◽

Kun Wei

Keyword(s):

Electron Microscopy ◽

Glycolic Acid ◽

Water Solubility ◽

Skin Diseases ◽

Biological Activities ◽

Drug Loading ◽

Synthesis Method ◽

Hacat Cells ◽

Scanning Calorimetry

Astaxanthin is a xanthophyll carotenoid with high beneficial biological activities, such as antioxidant function and scavenging oxygen free radicals, but its application is limited because of poor water solubility and low bioavailability. Here, we prepared and optimized poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with astaxanthin using the emulsion solvent evaporation technique and investigated the anti-photodamage effect in HaCaT cells. The four-factor three-stage Box–Behnken design was used to optimize the nanoparticle formulation. The experimental determination of the optimal nanoparticle size was 154.4 ± 0.35 nm, the zeta potential was 22.07 ± 0.93 mV, encapsulation efficiency was 96.42 ± 0.73% and drug loading capacity was 7.19 ± 0.12%. The physico-chemical properties of the optimized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo-gravimetric analyser. In vitro study exhibited the excellent cell viability and cellular uptake of optimized nanoparticles on HaCaT cells. The anti-photodamage studies (cytotoxicity assay, reactive oxygen species content and JC-1 assessment) demonstrated that the optimized nanoparticles were more effective and safer than pure astaxanthin in HaCaT cells. These results suggest that our PLGA-coated astaxanthin nanoparticles synthesis method was highly feasible and can be used in cosmetics or the treatment of skin diseases.

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Doxorubicin-loaded Fe3O4-ZIF-8 nano-composites for hepatocellular carcinoma therapy

Journal of Biomaterials Applications ◽

10.1177/0885328219836540 ◽

2019 ◽

Vol 33 (10) ◽

pp. 1373-1381 ◽

Cited By ~ 2

Author(s):

Chong Cheng ◽

Cheng Li ◽

Xulong Zhu ◽

Wei Han ◽

Jianhui Li ◽

...

Keyword(s):

Electron Microscopy ◽

Hepatocellular Carcinoma ◽

Cellular Uptake ◽

Laser Scanning ◽

Drug Loading ◽

Confocal Laser Scanning Microscope ◽

Confocal Laser ◽

Nano Composites ◽

High Drug ◽

High Drug Loading

Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers and has no effective therapeutic approaches. Chemotherapeutic drug doxorubicin (DOX) is widely used for HCC therapy, but its application is limited by the clinical toxicity. In the present study, an Fe3O4-ZIF-8 magnetic nano-composite was fabricated and used for DOX delivery for HCC therapy. The morphology, structure and property of Fe3O4-ZIF-8 nano-composites were evaluated by scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption isotherms studies. The drug release from DOX@Fe3O4-ZIF-8 was measured in pH 7.4 phosphate-buffered saline. The cellular uptake ability of DOX@Fe3O4-ZIF-8 into hepatocarcinoma cell line (MHCC97H) was visualized with a confocal laser scanning microscope. The effects of Fe3O4-ZIF-8, DOX and DOX@Fe3O4-ZIF-8 against MHCC97H cells were evaluated by CCK-8 assay and flow cytometry assay. Fe3O4-ZIF-8 nano-composites were synthesized and used as a nano-carrier for the delivery of DOX. Because of high drug loading property of ZIF-8, 1 mg Fe3O4-ZIF-8 nano-composites loaded 120 μg DOX when DOX@Fe3O4-ZIF-8 was synthesized in 30 mg/mL DOX solution. The cumulative DOX release curve showed a slow and sustained release pattern over time. The results of CCK-8 assay showed that Fe3O4-ZIF-8 was nontoxic to MHCC97H cells, and DOX@Fe3O4-ZIF-8 presented effective inhibiting effect on cell viability of MHCC97H cells. Cellular uptake assay showed that DOX@Fe3O4-ZIF-8 accumulated in both cytoplasm and nuclei. Moreover, because of valid drug accumulation, DOX@Fe3O4-ZIF-8 exhibited a good inducing effect on cell apoptosis of MHCC97H cells. In conclusion, based on the nontoxic and high drug loading capability of Fe3O4-ZIF-8, DOX@Fe3O4-ZIF-8 presented enhanced effects on HCC cells compared to free DOX, indicating its potential for the chemotherapy of HCC.

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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

Acta Biomaterialia ◽

10.1016/j.actbio.2015.01.039 ◽

2015 ◽

Vol 16 ◽

pp. 156-168 ◽

Cited By ~ 53

Author(s):

Helin Xu ◽

Dan Yang ◽

Cuifang Cai ◽

Jingxin Gou ◽

Yu Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Drug Loading ◽

In Vivo Evaluation ◽

High Drug ◽

Dual Responsive ◽

High Drug Loading ◽

Core Nanoparticles

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Preparation and In Vitro Cellular Uptake Assessment of Multifunctional Rubik-Like Magnetic Nano-Assemblies

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2019.16129 ◽

2019 ◽

Vol 19 (6) ◽

pp. 3301-3309

Author(s):

Xiawen Zheng ◽

Yuejian Chen ◽

Zhiming Wang ◽

Lina Song ◽

Yu Zhang ◽

...

Keyword(s):

Oleic Acid ◽

Folic Acid ◽

Cellular Uptake ◽

Hela Cells ◽

Drug Loading ◽

Superparamagnetic Iron Oxide ◽

Drug Carriers ◽

High Drug ◽

High Drug Loading

Through self-assembly of nanoparticles into high-order and stable structures of cubic clusters, high drug-loading rubik-like magnetic nano-assemblies (MNAs), possessing folic acid targeting and strong magnetism-enhanced cellular uptake capabilities, were built. In this study, the core of the cubic drug assemblies consisted of four monodisperse superparamagnetic iron oxide nanoparticles coated with layers of oleic acid (Fe3O4@OA), simultaneously encapsulating fluorescein, and Paclitaxol (Flu-MNAs and PTX-MNAs) for imaging and therapeutic applications. To enable preferential tumor cellular uptake by the nanocarriers, the outermost layer of Fe3O4 was functionalized with the new dual-oleic acid-polyethylene glycol-folic acid polymer (FA-PEG-Lys-OA2) as a “shell.” The drug carriers exhibited excellent stability and biocompatibility, and showed high drug loading and excellent magnetic response In Vitro. Furthermore, preliminary evaluations of the drug carriers with Hela cells showed effective cellular targeting capability. In addition, the cubic assemblies enhanced anticancer efficiency for Hela cells compared to bare drugs. Especially, the applied external magnetic field further improved the uptake of the vectors, and thereby enhanced the inhibitory effect. In brief, all these results suggested that cubic assemblies could serve as potential strategies for targeted anticancer therapies.

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Zirconium-Porphyrin PCN-222: pH-responsive Controlled Anticancer Drug Oridonin

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/3249023 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Xin Leng ◽

Hongliang Huang ◽

Wenping Wang ◽

Na Sai ◽

Longtai You ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Hepg2 Cells ◽

Drug Loading ◽

Annexin V ◽

Controlled Drug Release ◽

Dapi Staining ◽

High Drug ◽

High Drug Loading

Drug delivery carriers with a high drug loading capacity and biocompatibility, especially for controlled drug release, are urgently needed due to the side effects and frequent dose in the traditional therapeutic method. Guided by nanomaterials, we have successfully synthesized zirconium-based metal−organic frameworks, Zr-TCPP (TCPP: tetrakis (4-carboxyphenyl) porphyrin), namely, PCN-222, which is synthesized by solvothermal method. And it has been designed as a drug delivery system (DDS) with a high drug loading of 38.77 wt%. In our work, PCN-222 has achieved pH-sensitive drug release and showed comprehensive SEM, TEM, PXRD, DSC, FTIR, and N2 adsorption-desorption. The low cytotoxicity and good biocompatibility of PCN-222 were certificated by the in vitro results from an MTT assay, DAPI staining, and Annexin V/PI double-staining even cultivated L02 cells and HepG2 cells for 48h. Furthermore, Oridonin, a commonly used cancer chemotherapy drug, is adsorbed into PCN-222 via the solvent diffusion technique. Based on an analysis of the Oridonin release profile, results suggest that it can last for more than 7 days in vitro. And cumulative release rate of Ori at the 7 d was about 86.29% and 63.23% in PBS (pH 5.5 and pH 7.2, respectively) at 37°C. HepG2 cells were chosen to research the cytotoxicity of PCN-222@Ori and free Oridonin. The results demonstrated that the PCN-222@Ori nanocarrier shows higher cytotoxicity in HepG2 cells compared to Oridonin.

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Core–shell noble-metal@zeolitic-imidazolate-framework nanocarriers with high cancer treatment efficiency in vitro

Journal of Materials Chemistry B ◽

10.1039/c8tb03318h ◽

2019 ◽

Vol 7 (7) ◽

pp. 1050-1055 ◽

Cited By ~ 5

Author(s):

Liangcan He ◽

Kanglei Pang ◽

Wenwen Liu ◽

Yue Tian ◽

Lin Chang ◽

...

Keyword(s):

Drug Release ◽

Cancer Treatment ◽

Drug Loading ◽

Controlled Drug Release ◽

Core Shell ◽

Treatment Efficiency ◽

Zeolitic Imidazolate Framework ◽

High Drug ◽

High Drug Loading

Core–shell Au@zeolitic-imidazolate-framework nanocarriers with high drug-loading, controlled drug release properties, and high cancer treatment efficiency.

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Development, characterization and evaluation of the dissolution profile of sulfasalazine suspensions

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000200022 ◽

2015 ◽

Vol 51 (2) ◽

pp. 449-459 ◽

Cited By ~ 2

Author(s):

Mayre Aparecida Borges da Costa ◽

Ana Lucia Vazquez Villa ◽

Rita de Cássia da Silva Ascenção Barros ◽

Eduardo Ricci-Júnior ◽

Elisabete Pereira dos Santos

Keyword(s):

Particle Size ◽

Size Distribution ◽

Inflammatory Diseases ◽

Dissolution Behavior ◽

Dissolution Profile ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Neutral Media ◽

Sedimentation Volume

This paper reports the development, characterization and <italic>in vitro</italic>dissolution behavior of sulfasalazine suspensions for treatment of chronic intestinal inflammatory diseases. Three formulations were developed, from powdered sulfasalazine obtained from different suppliers. The sulfasalazine was characterized regarding concentration, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), particle size distribution, polydispersion and solubility. The suspensions were developed and characterized regarding pH, viscosity, density, particle size, sedimentation volume, concentration and dissolution. The pH values were slightly acidic. The method of preparing the suspensions reduced the particle sizes and made the size distribution more homogeneous. The dissolution studies showed that the sulfasalazine suspensions had low solubility in acidic media, but dissolve quickly, reaching levels of 85%, in neutral media or media containing 0.5% of surfactants such as polysorbate 80. Besides this, the sulfasalazine suspensions were classified as having immediate dissolution because they reached dissolution levels near 100% in 20 minutes.

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