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Cubosomes
RSC Advances · 2019 ·Vol. 9 ·期 11 ·6287-6298 · IF 3.049

Cubosomes with surface cross-linked chitosan exhibit sustained release and bioavailability enhancement for vinpocetine

Yuanfeng Wei,Jianjun Zhang,Yazhen Zheng,Yaxiang Gong,Meng Fu,Chengran Liu,Liang Xu,Changquan Calvin Sun,Yuan Gao,Shuai Qian

The present study aims to develop cubosomes with surface cross-linked chitosan for sustained drug delivery and enhanced oral bioavailability of vinpocetine (VPT). GMO based liquid cubosomes with VPT loading were prepared by the high pressure homogenization method. In order to enhance the anti-digestion effect, chitosan was cross-linked on cubosomes by the Schiff reaction, followed by solidification via spray drying. The obtained spray-dried cubosomes (chito-cubosomes) are spherical microspheres with nano-sized holes on the surface. After reconstitution, the particle size and zeta potential of chito-cubosomes were determined to be ∼250 nm and +35.9 mV, respectively. In comparison to unmodified liquid cubosomes, chito-cubosomes exhibited a significant anti-digestion effect with a typical sustained release profile. In comparison to a VPT suspension, liquid cubosomes showed a 2.5-fold higher Cmax and 3.0-fold higher AUC0–∞, while chito-cubosomes further enhanced bioavailability (5.0-fold) with prolonged MRT (2.2-fold) and delayed Tmax (2.8-fold). The results suggested that chito-cubosomes could be a promising drug carrier for enhancing oral absorption with sustained release behavior.

研究领域: 药剂学 · 药物递送系统
✓ 已验证 DOI PubMed 高影响因子
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LANGMUIR · 2019 · IF 3.683

pH Responsiveness of Hexosomes and Cubosomes for Combined Delivery of Brucea javanica Oil and Doxorubicin

Yawen Li,Angelina Angelova,Fangzhou Hu,Vasil M. Garamus,Changjun Peng,Na Li,Jianwen Liu,Dan Liu,Aihua Zou

We report pH-responsive liquid crystalline lipid nanoparticles, which are dual-loaded by Brucea javanica oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH = 7.4) to cubic (pH = 6.8) to emulsified microemulsion (pH = 5.3) phase transition with a therapeutic application in cancer inhibition. BJO is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an antitumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need for safe delivery carriers. Here, pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein–oleic acid–BJO–DOX) systems are determined by synchrotron small-angle X-ray scattering and the Langmuir film balance technique. The nanocarrier assemblies display good physical stability in the studied pH range and adequate particle sizes and ζ-potentials. Their interaction with model lipid membrane interfaces is enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO–DOX dual-loaded pH-switchable liquid crystalline nanoparticles are performed on the human breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines exhibit enhanced antitumor efficacy. The performed preliminary studies suggest a potential reversal of the resistance of the MCF-7/DOX cells to DOX. These results highlight the necessity for further understanding the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, and emulsified microemulsion inner organizations for therapeutic outcomes.

研究领域: 药学 · 纳米技术 · 癌症研究 · 药物递送系统 · 生物物理学
✓ 已验证 DOI PubMed 高影响因子
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BIOMEDICINE & PHARMACOTHERAPY · 2023 · IF 7.5

Cubosomes-assisted transdermal delivery of doxorubicin and indocyanine green for chemo-photothermal combination therapy of melanoma

Zhenzhen Chen,Qinbiao Huang,Yutong Song,Xianquan Feng,Lingjun Zeng,Zhihong Liu,Xiaomu Hu,Chun Tao,Lie Wang,Yafeng Qi,Hongtao Song

Melanoma is a highly aggressive form of skin cancer with limited therapeutic options. Chemo-photothermal combination therapy has demonstrated potential for effectively treating melanoma, and transdermal administration is considered the optimal route for treating skin diseases due to its ability to bypass first-pass metabolism and enhance drug concentration. However, the stratum corneum presents a formidable challenge as a significant barrier to drug penetration in transdermal drug delivery. Lipid-nanocarriers, particularly cubosomes, have been demonstrated to possess significant potential in augmenting drug permeation across the stratum corneum. Herein, cubosomes co-loaded with doxorubicin (DOX, a chemotherapeutic drug) and indocyanine green (ICG, a photothermal agent) (DOX-ICG-cubo) transdermal drug delivery system was developed to enhance the therapeutic efficiency of melanoma by improving drug permeation. The DOX-ICG-cubo showed high encapsulation efficiency of both DOX and ICG, and exhibited good stability under physiological conditions. In addition, the unique cubic structure of the DOX-ICG-cubo was confirmed through transmission electron microscopy (TEM) images, polarizing microscopy, and small angle X-ray scattering (SAXS). The DOX-ICG-cubo presented high photothermal conversion efficiency, as well as pH and thermo-responsive DOX release. Notably, the DOX-ICG-cubo exhibited enhanced drug permeation efficiency, good biocompatibility, and improved in vivo anti-melanoma efficacy through the synergistic effects of chemo-photothermal therapy. In conclusion, DOX-ICG-cubo presented a promising strategy for melanoma treatment.

研究领域: 药学 · 纳米技术 · 肿瘤学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2020 · IF 5.162

Adjuvant activities of CTAB-modified Polygonatum sibiricum polysaccharide cubosomes on immune responses to ovalbumin in mice

Zhenguang Liu,Haiyu Ni,Lin Yu,Shuwen Xu,Ruonan Bo,Tianxin Qiu,Pengfei Gu,TianYu Zhu,Jin He,Adelijiang Wusiman,Shaowu Zhu,Jiaguo Liu,Yuanliang Hu,Deyun Wang

Recently, the cubosomes have been widely studied as drug carriers. It has been described that cubosomes could further stimulate the immune response after carrying the immune enhancer. Polygonatum sibiricum polysaccharide (PSP), one of the most important biologically active ingredients of Polygonatum sibiricum , has been reported as an immunostimulant to improve immune responses. This study was aimed to observe the immunomodulation effects of ovalbumin (OVA) absorbed cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs/OVA). Firstly, the antigen uptake of CTAB-modified PSP-Cubs/OVA by macrophages was determined in vitro. After that, mice were immunized with CTAB-modified PSP-Cubs/OVA. The activation of dendritic cells in lymph nodes, activation of lymphocyte, ratios of CD4 + to CD8 + , the concentrations of OVA-specific IgG in serum and the cytokines concentrations were analyzed. As the results showed, CTAB-modified PSP-Cubs/OVA could promote the production of OVA-specific IgG in serum. The ratio of CD4 + to CD8 + in CTAB-modified PSP-Cubs/OVA group was significantly increased compared with other groups. CTAB-modified PSP-Cubs/OVA could significantly activate dendritic cells and promote lymphocyte proliferation. The results indicated that CTAB-modified PSP-Cubs/OVA could promote the secretion of related cytokines and the proliferation of lymphocytes, stimulate the cellular immune response and increase the level of humoral immunity. Above all, CTAB-modified PSP-Cubs had good adjuvant activity.

CAS / MDL: 57-09-0
研究领域: 免疫学 · 药剂学 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Biomedical Nanotechnology · 2013 ·Vol. 9 ·期 10 ·1784-1793 · IF 5.256

Protein-Bearing Cubosomes Prepared by Liquid Precursor Dilution: Inner Ear Delivery and Pharmacokinetic Study Following Intratympanic Administration

Liu Hongzhuo,Wang Yan,Wang Qifang,Li Zhen,Zhou Yanyan,Zhang Yusheng,Li Sanming

This study aims to design self-assembled cubic liquid crystalline nanoparticles (cubosomes) to enhance inner ear bioavailability of earthworm fibrinolytic enzyme (EFE). The cubosomes were prepared using a liquid precursor mixture containing glyceryl monooleate, hydrotrope propylene glycol, and F127 as stabilizer. Submicron-size particles (100 nm to 200 nm) with slight negative charge formed spontaneouly upon dilution of the liquid precursors. Small-angle X-ray scattering (SAXS) results demonstrated that the formation of cubsomses largely depended on the hydration level of liquid precursor and the encapsulation of highly hydrophilic EFE induced the phase transition of the cubosome. The encapsulatoin efficiency of EFE in cubosomes was 79.6% and their cubic ultrastructure were confirmed by TEM. In vitro cell toxicity results showed that the viability of L929 cells decreased by increasing the concentration of nanoparticles. Octadecyl rhodamine B chloride (R18) labeled cubosomes were identified in the basal turn of the scala tympani and middle portion of the cochlea after 30 min post intratympanic administration, indicating that cubosomes could permeate through the RWM. The AUC0 h–24 h of EFE administrated as EFE cubosomes was 2.6-fold in cochlear fluid compared to those applied by free drug via the intratympanic route. In conclusion, self-assembled liquid crystalline nanoparticles provide a promising protein vehicle for effective inner ear drug delivery.

研究领域: 药学 · 纳米技术 · 药物递送系统 · 耳鼻喉科学
✓ 已验证 DOI PubMed 高影响因子
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ADVANCED MATERIALS · 2024 ·Vol. 36 ·期 27 ·2313920 · IF 27.4

A Versatile Synthesis Platform Based on Polymer Cubosomes for a Library of Highly Ordered Nanoporous Metal Oxides Particles

Wenhe Xie,Xinyu Huang,Chengcheng Zhu,Fengluan Jiang,Yu Deng,Bingjie Yu,Limin Wu,Qin Yue,Yonghui Deng

Polymer cubosomes (PCs) have well-defined inverse bicontinuous cubic mesophases formed by amphiphilic block copolymer bilayers. The open hydrophilic channels, large periods, and robust physical properties of PCs are advantageous to many host–guest interactions and yet not fully exploited, especially in the fields of functional nanomaterials. Here, the self-assembly of poly(ethylene oxide)- block -polystyrene block copolymers is systematically investigated and a series of robust PCs is developed via a cosolvent method. Ordered nanoporous metal oxide particles are obtained by selectively filling the hydrophilic channels of PCs via an impregnation strategy, followed by a two-step thermal treatment. Based on this versatile PC platform, the general synthesis of a library of ordered porous particles with different pore structures 3 ¯ $\bar{3}$ 3 ¯ $\bar{3}$ , tunable large pore size (18–78 nm), high specific surface areas (up to 123.3 m 2 g −1 for WO 3 ) and diverse framework compositions, such as transition and non-transition metal oxides, rare earth chloride oxides, perovskite, pyrochlore, and high-entropy metal oxides is demonstrated. As typical materials obtained via this method, ordered porous WO 3 particles have the advantages of open continuous structure and semiconducting properties, thus showing superior gas sensing performances toward hydrogen sulfide.

研究领域: 材料科学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2019 · IF 4.213

Optimization of preparation conditions for CTAB-modified Polygonatum sibiricum polysaccharide cubosomes using the response surface methodology and their effects on splenic lymphocytes

Haiyu Ni,Shuwen Xu,Pengfei Gu,Adelijiang wusiman,Yue Zhang,Tianxin Qiu,Zhenguang Liu,Han Ni,Yuanliang Hu,Jiaguo Liu,Yi Wu,Deyun Wang

This study aimed to optimize the preparation conditions for cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs) by response surface methodology (RSM). Glyceryl-monooleate (GMO) was used as the lipid base for the cubosomes. The optimal preparation conditions of CTAB-modified PSP-Cubs were as follows: the mass percentage of PSP to GMO (X 1 ), Poloxamer 407 (F127) to GMO (X 2 ) and water to GMO (X 3 ) was 1.4%, 9% and 50%, respectively. The encapsulation efficiency (EE) of CTAB-modified PSP-Cubs under the experimental conditions was 62.4 ± 3.6%, which was close to our predicted value. The particle size, polydispersity index (PDI) and zeta potential of CTAB-modified PSP-Cubs were 427.7 ± 8.0  nm , 0.236 ± 0.024 and 19.2 ± 0.4 mV, respectively. Specific modifications were able to slow down in vitro release behaviors and reduce cytotoxicity to some extent. The effects of CTAB-modified PSP-Cubs on splenic lymphocytes were also investigated. When splenic lymphocytes were treated with CTAB-modified PSP-Cubs together with LPS or PHA , the results showed more favorable effects on cellular proliferation than blank cubosomes or free PSP at certain concentrations.

CAS / MDL: 57-09-0
研究领域: 药剂学 · 免疫学 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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