Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery

Prabaharan, M.; Grailer, Jamison; Pilla, Srikanth; Steeber, Douglas A.; Gong, Shaoqin

doi:10.1016/j.biomaterials.2009.07.020

Cited by 357 publications

(285 citation statements)

References 29 publications

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“…However, the drug-loaded NPs were mainly taken up by cells via the endocytosis pathway and then exerted the antitumor activity after the drug molecules were released from the NPs. 54 CI 50 value of the TAT PTX/TOS-CDDP SLNs was the lowest (0.646), indicating co-delivery of PTX and TOS-CDDP by TATmodified SLNs had evident superiority as compared with free drug combination and unmodified PTX/TOS-CDDP SLNs.…”

mentioning

confidence: 95%

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

Liu¹,

Liang²,

Liu³

et al. 2017

IJN

103

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Background Cervical cancer is a major world health problem for women. Currently, cancer research focuses on improving therapy for cervical cancer using various treatment options such as co-delivery of chemotherapeutic agents by nanocarriers. Purpose The aim of this study was to develop trans-activating transcriptional activator (TAT)-modified solid lipid nanoparticles (SLNs) for co-delivery of paclitaxel (PTX) and α-tocopherol succinate-cisplatin prodrug (TOS-CDDP) (TAT PTX/TOS-CDDP SLNs) in order to achieve synergistic antitumor activity against cervical cancer. Methods Lipid prodrug of CDDP (TOS-CDDP) and TAT-containing polyethylene glycol-distearoyl-phosphatidylethanolamine (TAT-PEG-DSPE) were synthesized. TAT PTX/TOS-CDDP SLNs were prepared by emulsification and solvent evaporation method. Physicochemical characteristics of SLNs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells. Results TAT PTX/TOS-CDDP SLNs could be successfully internalized by HeLa cells and showed a synergistic effect in the suppression of cervical tumor cell growth. They exhibited high tumor tissue accumulation, superior antitumor efficiency, and much lower toxicity in vivo. Conclusion The present study indicates that the co-delivery system provides a promising platform as a combination therapy for the treatment of cervical cancer, and possibly other types of cancer as well.

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mentioning

confidence: 95%

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

Liu¹,

Liang²,

Liu³

et al. 2017

IJN

103

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“…It is noted that copolymers such as dendrimers (Medina & El-Sayed, 2009;Pan et al, 2009;Abderrezak et al, 2012), linear-b-dendritic block copolymers (Wurm & Frey, 2011), star block copolymers (Prabaharan et al, 2009a) and brush copolymers (Prabaharan et al, 2009b;Yan et al, 2009) have been studied as vehicles for drug loading and delivery. In comparison with linear polymers, these branched polymers have a greater effect on the physico-chemical characteristics of the polymer itself as well as drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

et al. 2014

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(2015) Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin, Drug Delivery, 22:1, 58-68, DOI: 10.3109/10717544.2014 Methods: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly ("-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and "-caprolactone as raw materials. Its structure was characterized by 1 H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out. Results: Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 Â 10 5 times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model (R 2 abj ¼ 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT 0-1 , t 1/2z and AUC 0-1 of Curcuminloaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution. Conclusions: The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR.

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“…This drug loading efficiency is higher than the one in our previous study, where presnisolone was loaded simultaneously with core cross-linking [45]. It is well-known that an acid-sensitive hydrazone bond can undergo hydrolysis under acidic conditions [47], which releases pristine DOX from PEO-b-PGMA-(N 3 )-DOX. To verify whether CCL prodrug micelles could effectively protect DOX from premature release and exhibit pH and reduction Figure 6.…”

Section: Dox Releasementioning

confidence: 60%

Redox-responsive core cross-linked prodrug micelles prepared by click chemistry for pH-triggered doxorubicin delivery

Cao¹,

Le²,

Thi³

et al. 2017

Express Polym. Lett.

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Abstract.A pH-triggered drug delivery system of degradable core cross-linked (CCL) prodrug micelles was prepared by click chemistry. Doxorubicin conjugated block copolymers of azido functional poly(ethylene oxide)-b-poly(glycidyl methacrylate) were synthesized by the combination of RAFT polymerization, epoxide ring-opening reaction, and acid-cleavable hydrazone linkages. The CCL prodrug micelles were produced by the reaction of dipropargyl 3,3′-dithiodipropionate and dipropargyl adipate cross-linking agents with the azido groups of the micellar core via alkyne-azide click reaction, which were denoted as CCL/SS and CCL/noSS, respectively. The TEM images of CCL/SS prodrug micelles showed a spherical shape with the average diameter of 61.0 nm from water, and the shape was maintained with an increased diameter upon dilution with 5-fold DMF. The high DOX conjugation efficiency was 88.4%. In contrast to a very slow DOX release from CCL/SS prodrug micelles under the physiological condition (pH 7.4), the drug release is much faster (90%) at pH 5.0 and 10 mM of GSH after 96 h. The cytotoxicity test and confocal laser scanning microscopy analysis revealed that CCL/SS prodrug micelles had much enhanced intracellular drug release capability in HepG2 cells than CCL/noSS prodrug micelles.

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Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH-sensitive hydrazone bond for tumor-targeted drug delivery

Cited by 357 publications

References 29 publications

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Redox-responsive core cross-linked prodrug micelles prepared by click chemistry for pH-triggered doxorubicin delivery

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