In Vitro and In Vivo Safety Evaluation of Biodegradable Self-Assembled Monomethyl Poly (Ethylene Glycol)–Poly(ε-Caprolactone)–Poly (Trimethylene Carbonate) Micelles

Yang, Xi; Cao, Dan; Wang, Ning; Sun, Lu; Li, Ling; Nie, Shihong; Wu, Qinjie; Liu, Xinyu; Yi, Cheng; Gong, Changyang

doi:10.1002/jps.23800

Cited by 15 publications

(10 citation statements)

References 49 publications

(51 reference statements)

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“…Our previous work successfully synthesized the MPEG-P(CL- co -TMC) copolymers. The in vitro and in vivo safety evaluation demonstrated that the MPEG-P(CL- co -TMC) micelles could be a safe candidate for application in hydrophobic drug dilivery systems (DDSs) 37 . The MPEG-P(CL- co -TMC) micelles form a spherical core-shell architecture where MPEG of amphiphilic molecules forms the exterior shell, while the hydrophobic segmnt (the core) is random copolymer between the two hydrophobic monomers, TMC and ε-CL.…”

Section: Discussionmentioning

confidence: 99%

Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo

Yang

Wang

et al. 2015

Sci Rep

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134

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To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.

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Section: Discussionmentioning

confidence: 99%

Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo

Yang

Wang

et al. 2015

Sci Rep

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134

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“…164 PEGylated block copolymers forming micelles show extremely low cytotoxicity both in vitro and in vivo. [165][166][167] Moreover, due to their stealth property, PEGylated drug carriers tend to circulate longer in the bloodstream, avoiding phagocytosis, although recent reports revealed that multiple doses induce anti-PEG IgM production, resulting in an accelerated blood clearance (ABC) phenomenon of the PEGylated carriers. 168,169 PGlu-b-PTMC ( Figure 1H), which generally forms vesicles, exhibits no cytotoxicity, but provokes oxidative stress against hepatocellular carcinoma cells (HepG2) and human lymphoblast cells (TK6) and slightly high cytokine production in lung epithelial cells (A549).…”

Section: Drug Delivery and Theranosticsmentioning

confidence: 99%

Poly(trimethylene carbonate)-based polymers engineered for biodegradable functional biomaterials

2016

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Aliphatic polycarbonates have drawn attention as biodegradable polymers that can be applied to a broad range of resorbable medical devices. In particular, poly(trimethylene carbonate) (PTMC), its copolymers, and its derivatives are currently studied due to their unique degradation characteristics that are different from those of aliphatic polyesters. Furthermore, their flexible and hydrophobic nature has driven the application of PTMC-based polymers to soft tissue regeneration and drug delivery. This review presents the diverse applications and functionalization strategies of PTMC-based materials in relation to recent advances in medical technologies and their subsequent needs in clinical settings.

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“…Major organs were examined macroscopically, and lung, liver, and spleen were fixed and stained with H&E for histopathological examination (38). We determined that the dose used in this study was well tolerated by the experimental mice and had no toxicity.…”

Section: Methodsmentioning

confidence: 99%

Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid

Comba

Almada

Tolosa

et al. 2016

Journal of Biological Chemistry

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Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor gliomaassociated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AAinduced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches.

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In Vitro and In Vivo Safety Evaluation of Biodegradable Self-Assembled Monomethyl Poly (Ethylene Glycol)–Poly(ε-Caprolactone)–Poly (Trimethylene Carbonate) Micelles

Cited by 15 publications

References 49 publications

Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo

Curcumin-Encapsulated Polymeric Micelles Suppress the Development of Colon Cancer In Vitro and In Vivo

Poly(trimethylene carbonate)-based polymers engineered for biodegradable functional biomaterials

Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid

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