Delivery of anticancer drug using pH-sensitive micelles from triblock copolymer MPEG-b-PBAE-b-PLA

Yang, Chufen; Xue, Zhaolin; Liu, Yinglin; Xiao, Jiayu; Chen, Jingrui; Zhang, Lijuan; Guo, Juan; Lin, Wenjing

doi:10.1016/j.msec.2017.12.003

Cited by 50 publications

(39 citation statements)

References 46 publications

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“…The results showed that the optimal drug loading efficiency was obtained at a ratio of PTX and copolymer 13:40 (≈1:3). According to previous studies, the micelles with longer hydrophobic segment have higher drug loading content and entrapment efficiency [29,38,39]. Under the same drug feed ratio test condition, AdP-2 exhibited higher drug entrapping ability than AdP-1, due to the longer hydrophobic content of AdP-2.…”

Section: Resultsmentioning

confidence: 79%

Nano-Carriers Based on pH-Sensitive Star-Shaped Copolymers for Drug-Controlled Release

et al. 2019

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Polymeric nano-carriers are considered as promising tools in biomedical applications due to multiple attractive characteristics including their low toxicity, high loading capacity, controlled drug release capabilities, and highly tunable chemical properties. Here, a series of pH-sensitive star-shaped copolymers, Ad-P[(EMA-co-MAA)-b-PPEGMA]4, was prepared via electron transfer atom radical polymerization (ARGETE ATRP) and selective hydrolysis. These star-shaped copolymers can be self-assembled into micelles (Dh = 150–160 nm) and their critical micelle concentrations (CMC) were estimated to be 3.9–5.0 mg/L. The pH-sensitiveness of the micelles was evidenced by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The maximal paclitaxel (PTX) loading efficiency (DLC) and entrapment efficiency (EE) were 18.9% and 36%, respectively. In vitro release studies revealed that about 19% of the PTX released at an acidic condition of pH 1.2 over 70 h, whereas more than 70% was released within the same time interval at pH 6.8. In vitro cytotoxicity suggested that the low cytotoxicity of the blank micelles, while the PTX-loaded micelles providing the cytotoxicity close to that of free PTX. These results indicated that this novel pH-sensitive nano-carriers have great potential applications for oral drug-controlled release.

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Section: Resultsmentioning

confidence: 79%

Nano-Carriers Based on pH-Sensitive Star-Shaped Copolymers for Drug-Controlled Release

et al. 2019

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“…The blank mixed micelles formed from PDEAEMA-PPEGMA and PCL-PPEGMA were prepared by the solvent evaporation method [17]. The mixed polymers (PDEAEMA-PPEGMA 15 mg, PCL-PPEGMA 15 mg) were dissolved into 10 mL of acetone and added to 30 mL of deionized water drop by drop under agitation; then, acetone was volatilized under stirring at 25 • C for 24 h. After being filtered by a 0.45 µm membrane filter, the solution of blank mixed micelles with a concentration of 1 mg/mL was obtained.…”

Section: Preparation and Characterization Of The Blank And Dox-loadedmentioning

confidence: 99%

“…The different pH-sensitive polymeric micelles can be designed for release to different organs, tissues, and cells in a well-controlled manner. As for delivering intravenous anticancer drugs, it tends to require that the pH-triggered amphiphilic copolymers micelles remain stable in normal tissues (pH 7.4), while releasing the anticancer drugs quickly in tumor tissue (pH 5.0-6.5) [16][17][18][19][20]. Although great achievements have been made, there are still several significant parameters that need to be further improved and optimized, such as the micellar targetability, stability, longevity, drug loading capacity, particle sizes, and size distribution.…”

Section: Introductionmentioning

confidence: 99%

pH-Sensitive Mixed Micelles Assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for Doxorubicin Delivery: Experimental and DPD Simulations Study

et al. 2020

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To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (N,N-diethylaminoethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and polycaprolactone-b-poly (poly(ethylene glycol) methyl ether methacrylate) (PCL-PPEGMA), which were synthesized and confirmed by 1H NMR and gel permeation chromatographic (GPC). The critical micelle concentration (CMC) values of the prepared mixed micelles were low, and the micellar sizes and zeta potentials of the blank mixed micelles demonstrated good pH-responsive behavior. Combined experimental techniques with dissipative particle dynamics (DPD) simulation, the particle sizes, zeta potentials, drug loading content (LC), encapsulation efficiency (EE), aggregation morphologies, and doxorubicin (DOX) distribution of the mixed micelles were investigated, and the high DOX-loading capacity of the mixed micelles was found. Both in vitro DOX release profiles and DPD simulations of the DOX dynamics release process exhibited less leakage and good stability in neutral conditions and accelerated drug release behavior with a little initial burst in slightly acidic conditions. Cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles had good biocompatibility, and DOX-loaded mixed micelles revealed certain cytotoxicity. These results suggest that the drug-loaded mixed micelles that consisted of the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA can be new types of pH-responsive well-controlled release anticancer drug delivery mixed micelles.

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“…The pyrene was used as a probe to determine the CMC value of the polymer by fluorescence spectrometer. In general, the CMC value can reflect the self-assembly ability of the polymer to form micelles, and a lower CMC value is desired for increasing micellar stability in the blood stream [30,31]. From Figure 3, the CMC values of the three polymers were determined from the crossover points ranging from 5.0 to 11.2 mg/L, consistent with the high stability of polymer micelles; the CMC values of polymer 1, polymer 2 and polymer 3 were 11.2 mg/L, 8.7 mg/L, and 5.0 mg/L, respectively.…”

Section: Self-assembly Of Amphiphilic Polymermentioning

confidence: 99%

Biodegradable Redox-Sensitive Star Polymer Nanomicelles for Enhancing Doxorubicin Delivery

Guo

Wen

et al. 2019

Nanomaterials

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A typical amphiphilic star polymer adamantane-[poly(lactic-co-glycolic acid)-bis(2-carboxyethyl) sulfide-poly(ethylene glycol) monomethyl ether)]4 with a specific hydrophilic/redox-sensitive/hydrophobic structure was designed and synthesized through ring opening and esterification reactions. The self-assembled nanomicelles were used as doxorubicin (DOX) delivery vehicles with suitable critical micelle concentrations (5.0 mg/L). After the drug being loaded, drug-loaded micelles showed good drug-loading efficiency (10.39%), encapsulation efficiency (58.1%), and drug release (up to 60%) under simulated biological environment conditions. In addition, the backbone structure of the biodegradable polymer was easily hydrolyzed by the action of biological enzymes. As expected, cell-based studies showed that the designed polymer micelles possessed good biocompatibility (a survival rate of 85% for NH-3T3 cells). Moreover, the drug (DOX) still maintained good anti-cancer effects after being loaded, which caused 40% of MCF-7 cells to survive. These redox-sensitive micelles showed anti-tumor therapeutic potential.

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Delivery of anticancer drug using pH-sensitive micelles from triblock copolymer MPEG-b-PBAE-b-PLA

Cited by 50 publications

References 46 publications

Nano-Carriers Based on pH-Sensitive Star-Shaped Copolymers for Drug-Controlled Release

Nano-Carriers Based on pH-Sensitive Star-Shaped Copolymers for Drug-Controlled Release

pH-Sensitive Mixed Micelles Assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for Doxorubicin Delivery: Experimental and DPD Simulations Study

Biodegradable Redox-Sensitive Star Polymer Nanomicelles for Enhancing Doxorubicin Delivery

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