Redox-sensitive hyaluronic acid–paclitaxel conjugate micelles with high physical drug loading for efficient tumor therapy

2015 ◽  
Vol 6 (46) ◽  
pp. 8047-8059 ◽  
Author(s):  
Tingjie Yin ◽  
Jing Wang ◽  
Lifang Yin ◽  
Linjia Shen ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Drug Release ◽  
Cellular Uptake ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Drug Conjugates ◽  
Self Assembled ◽  
Polymer Drug Conjugates

Characterization of targeted redox-sensitive micelles self-assembled from polymer–drug conjugates exhibiting conspicuous drug loading capabilities, selective cellular uptake, rapid intracellular disassembly and drug release is presented.

scholarly journals Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Heng Mei ◽  
Jing Li ◽  
Shengsheng Cai ◽  
Xuequan Zhang ◽  
Wenqiang Shi ◽  
...  
Keyword(s):  
Drug Loading ◽  
Tumor Therapy ◽  
Ros Generation ◽  
Drug Conjugates ◽  
Tocopheryl Succinate ◽  
Carrier Free ◽  
Negative Surface ◽  
Inert Carrier ◽  
Self Assembled

Abstract Unsatisfactory drug loading capability, potential toxicity of the inert carrier and the limited therapeutic effect of a single chemotherapy drug are all vital inhibitory factors of carrier-assisted drug delivery systems for chemotherapy. To address the above obstacles, a series of carrier-free nanoplatforms self-assembled by dual-drug conjugates was constructed to reinforce chemotherapy against tumors by simultaneously disrupting intratumoral DNA activity and inhibiting mitochondria function. In this nanoplatform, the mitochondria-targeting small-molecular drug, α-tocopheryl succinate (TOS), firstly self-assembled into nanoparticles, which then were used as the carrier to conjugate cisplatin (CDDP). Systematic characterization results showed that this nanoplatform exhibited suitable particle size and a negative surface charge with good stability in physicochemical environments, as well as pH-sensitive drug release and efficient cellular uptake. Due to the combined effects of reactive oxygen species (ROS) generation by TOS and DNA damage by CDDP, the developed nanoplatform could induce mitochondrial dysfunction and elevated cell apoptosis, resulting in highly efficient anti-tumor outcomes in vitro. Collectively, the combined design principles adopted for carrier-free nanodrugs construction in this study aimed at targeting different intracellular organelles for facilitating ROS production and DNA disruption can be extended to other carrier-free nanodrugs-dependent therapeutic systems.

scholarly journals CARMUSTINE LOADED LACTOFERRIN NANOPARTICLES DEMONSTRATES AN ENHANCED ANTIPROLIFERATIVE ACTIVITY AGAINST GLIOBLASTOMA IN VITRO

2018 ◽  
Vol 10 (6) ◽  
pp. 234 ◽  
Author(s):  
Harikiran Athmakur ◽  
Anand Kumar Kondapi
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Cellular Uptake ◽  
Stable Distribution ◽  
Drug Loading ◽  
Glioblastoma Cells ◽  
Treatment Regimens ◽  
Microscopic Studies

Objective: Despite sophisticated treatment regimens, there is no significant improvement in the mortality rates of glioblastoma due to insufficient dosage delivery, reoccurrence of tumors, higher systemic toxicity, etc. Since brain endothelial cells and glioblastoma cells express lactoferrin receptors, a target-specific drug delivery vehicle was developed using lactoferrin itself as a matrix, into which carmustine was loaded. The objective was to use carmustine loaded lactoferrin nanoparticles (CLN) to achieve higher therapeutic efficacy and target specificity compared to free carmustine.Methods: CLN were prepared using the Sol-oil method. The nanoparticles prepared were characterized for their size, shape, polydispersity, and stability using FESEM and DLS methods. Drug loading and drug releasing efficiencies were also estimated. Further, cellular uptake of nanoparticles and their antiproliferative efficacy against glioblastoma cells were evaluated.Results: Characterization of CLN showed that they were spherical with ≤ 41 nm diameter and exhibited homogeneously dispersed stable distribution. Loading efficiency of carmustine in CLN was estimated to be 43±3.7 %. Drug release from the nanoparticles was pH dependent with the maximum observed at pH 5. At physiological and gastric pH, drug release was lower, whereas maximum release was observed at endocytotic vesicular and around tumor extracellular pH. Confocal microscopic studies showed an active cellular uptake of nanoparticles. Results of antiproliferative analysis substantiated a higher antiproliferative effect for CLN compared to free carmustine.Conclusion: The results of the study demonstrated that CLN serves as a vital tool, in designing an effective treatment strategy for targeted drug delivery to glioblastoma.

scholarly journals Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinfeng Shi ◽  
Yali Ren ◽  
Jiaqi Ma ◽  
Xi Luo ◽  
Jiaxin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hyaluronic Acid ◽  
Drug Release ◽  
Lung Metastasis ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Systemic Toxicity ◽  
Migration And Invasion ◽  
Stimuli Responsive ◽  
Cd44 Targeting

Abstract Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery

2020 ◽  
Vol 20 ◽  
Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Tilak R. Bhardwaj ◽  
Rajesh K. Singh
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Drug Release ◽  
Anticancer Agents ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Specific Treatment ◽  
Drug Conjugates ◽  
Polymer Drug Conjugates

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.

HYALURONIC ACID-DOCETAXEL CONJUGATE LOADED NANOLIPOSOMES FOR TARGETING TUMOR CELLS

2020 ◽  
pp. 88-99
Author(s):  
MULUNEH FROMSA SEIFU ◽  
LILA KANTA NATH ◽  
DEBASHIS DUTTA
Keyword(s):  
Hyaluronic Acid ◽  
Glial Cells ◽  
Cellular Uptake ◽  
Drug Loading ◽  
Microscopic Investigation ◽  
In Vitro Cytotoxicity ◽  
Scanning Calorimetry ◽  
Anticancer Efficacy ◽  
Apoptotic Effect

Objective: Docetaxel (DTX), a potent anticancer drug, is suffering from non-specificity and drug resistance as major limitations. In this investigation, we developed Hyaluronic acid (HA)-Docetaxel conjugate (HA-DTX) loaded nanoliposomes to target cancer cells via passive and active targeting approaches. Methods: HA-DTX was synthesized and characterized by UV-Visible spectrophotometry, FT-IR spectroscopy, 1H NMR spectroscopy, Differential scanning calorimetry and X-ray diffraction and then loaded into nanoliposomes (L-NLs) by thin-film hydration method. L-NLs were characterized physicochemically and evaluated for anticancer efficacy by in vitro cytotoxicity study in glioma cells (C6 glial cells); cellular uptake and apoptotic effect were investigated by fluorescence microscopy. Results: HA-DTX was successfully synthesized; L-NLs had an average size of 123.0±16.53 nm, polydispersity index of 0.246±0.01 and zeta potential of 44.4±6.79 mV. Also, L-NLs exhibited 90.54%±4.22 of drug loading efficiency and 2.68%±0.12 of drug loading, releasing about 57.72%±1.17 at pH 5.2 and only 14.14%±1.32 at pH 7.4 after 48 h. No significant change instability was observed after storage at 5 °C±3 °C as well as at 25 °C±2 °C/60% RH±5% RH for 6 mo. The cytotoxicity effect of L-NLs was higher by 10% that of marketed formulation at 10 µg/ml docetaxel concentration. Fluorescence microscopic investigation showed that more cellular uptake and apoptotic effect were observed in L-NLs treated C6 glial cells than in those treated with the marketed formulation. Conclusion: HA-DTX loaded nanoliposomes enabled docetaxel to target C6 glial cells with better efficacy and might be effective to treat glioma.

Glutathione-adaptive peptide amphiphile vesicles rationally designed using positionable disulfide-bridges for effective drug transport

2020 ◽  
Vol 11 (28) ◽  
pp. 4547-4556
Author(s):  
Hayeon Kim ◽  
Inhye Kim ◽  
Jun Ho Hwang ◽  
Jaehyun Park ◽  
Hyungju Ahn ◽  
...  
Keyword(s):  
Drug Release ◽  
Tumor Cells ◽  
Drug Transport ◽  
Drug Loading ◽  
Effective Drug ◽  
Peptide Amphiphiles ◽  
Disulfide Bridges ◽  
Peptide Amphiphile ◽  
Disulfide Linkages ◽  
Self Assembled

The drug loading/releasing capability of GSH-responsive nanovesicles self-assembled from peptide amphiphiles was controlled by varying the location and number of disulfide-linkages in the peptide for the selective drug-release into tumor cells.

Well-defined diblock brush polymer–drug conjugates for sustained delivery of paclitaxel

2015 ◽  
Vol 3 (7) ◽  
pp. 1078-1084 ◽  
Author(s):  
Jiong Zou ◽  
Yun Yu ◽  
Yukun Li ◽  
Wei Ji ◽  
Chih-Kuang Chen ◽  
...  
Keyword(s):  
Drug Release ◽  
Release Profile ◽  
Therapeutic Effects ◽  
Sustained Delivery ◽  
Drug Release Profile ◽  
Drug Conjugates ◽  
Brush Polymer ◽  
Polymer Drug Conjugates

The synthesis, characterization and property studies of paclitaxel (PTXL)-containing brush polymer–drug conjugates (BPDCs) are presented and the influence of grafting structures of BPDCs on their assembly behaviour, drug release profile and therapeutic effects is discussed in this article.

Preparation and Characterization of Cyclophosphamide-Loaded Chitosan Microspheres

2012 ◽  
Vol 621 ◽  
pp. 130-133
Author(s):  
Yi Lin Ding ◽  
Su Su Ding ◽  
Guo Fang Ding
Keyword(s):  
Drug Release ◽  
Anticancer Agent ◽  
Loading Rate ◽  
Drug Loading ◽  
Average Diameter ◽  
Uv Spectrophotometry ◽  
Chitosan Microspheres ◽  
Dialysis Bag

Chitosan microspheres were prepared by using a cross linking agent combined with an emulsion technique. Cyclophosphamide was loaded as an anticancer agent. Obtained microspheres were spherical and regular, with a smooth surface morphology, having an average diameter of 15.7±9.0μm. After preparation, the drug-loading rate and entrapment rate of cyclophosphamide was investigated by UV spectrophotometry. Drug release was tested in vitro in a dynamic dialysis system with a dialysis bag. The chitosan microspheres prepared were proved to have good drug release profiles.

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