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Self-assembled nanoparticles based on poly(ethylene glycol)-diosgenin prodrugs for co-delivery of anticancer drugs
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
prostate cancer and leukemia, etc. Unfortunately, the clinical application of PS has been hampered due to its poor water-solubility and relatively short half-life. To overcome the hurdle, the self-assembled nanoparticles based on eightarm-polyethylene glycol–pterostilbene (8arm-PEG-PS) conjugates were first presented. The 8arm-PEG-PS conjugates were synthesized by anesterification reaction between the carboxyl group of 8arm-polyethylene glycol and the hydroxyl group of PS. Then, they self-assembled into nanoparticles (Figure 1) to improve their pharmacological profiles. The nanoparticles have a small size (~ 100 nm) and exhibited significantly high water solubility and excellent in vitro anticancer activity compared with free PS. In vivo study demonstrated the superior therapeutic effect of nanoparticles on inhibition of tumor growth with lower systemic toxicity. On the basis of these results, we believe that the8arm-PEG-PS nanoparticles have great promise toward cancer therapy.
551
Figure 1. The synthesis of the amphiphilic phospholipid-mimicking prodrugs (a). Illustration of mPEG-Diosgenin nanoparticles encapsulated DHA for codelivery (b). TEM images of mPEG-Diosgenin encapsulate DHA nanoparticles. Inset: single nanoparticle TEM image at higher resolution (c). http://dx.doi.org/10.1016/j.nano.2015.12.292
Self-assembled nanoparticles based on α-tocopherol succinate-modified heparin for targeted delivery of paclitaxel Xiaoye Yang, Guangxi Zhai⁎, Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, China ⁎Corresponding author. E-mail address: [email protected] (G. Zhai)
Figure 1. Synthesis of eight-arm-polyethylene glycol-PS. TEM of nanoparticles.
http://dx.doi.org/10.1016/j.nano.2015.12.291
Self-assembled nanoparticles based on poly(ethylene glycol)-diosgenin prodrugs for co-delivery of anticancer drugs Chunxiao Li, Lin Dai, Kefeng Liu, Jiandu Lei⁎, Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing, P.R. China ⁎Corresponding author. E-mail address: [email protected] (J. Lei) Diosgenin is a steroidal saponin from a therapeutic herb, fenugreek. It is reported to be an important steroidal metabolite used as a starting material for the synthesis of antitumor drugs, as it exhibits estrogenic activity. Recently, a series of preclinical and mechanistic studies have shown great potential of diosgenin in the therapy for cancer. However, clinical application of diosgenin in cancer therapy is limited due to undesirable pharmaceutical characteristics such as its consequently poor solubility, relatively short half-life, and low bioavailability. In this study, we proposed to synthesize an amphiphilic phospholipidmimicking prodrugs system mPEG-Diosgenin by using methoxy poly(ethylene glycol). The prodrugs formed stable liposome-like nanoparticles with a high diosgenin loading content and no burst release in aqueous solution. In addition, they can be used as nanocarriers for co-delivery of another anticancer drug dihydroartemisinin (DHA) by a simple nanoprecipitation method. The obtained nanoparticles possessed appropriate size, high drug loading efficiency of diosgenin and DHA, slowly release drugs, higher the blood circulation half-time, and high synergistic effects. Hence, the mPEG-Diosgenin nanoparticle is a promising drug delivery system for cancer therapy.
To realize the efficient delivery of chemotherapeutic agents to tumor sites, numerous advanced vehicles have been investigated. Among them, self-assembled nanoparticles based on amphiphilic polymers have gained considerable interest. In this study, heparin was utilized as the hydrophilic backbone in view of its unique biological and physiochemical characterizations, especially the anti-angiogenesis and anti-metastasis activities. α-Tocopherol succinate was grafted to the backbone via coupling reaction, producing a novel amphiphilic polymer, α-tocopherol succinate modified heparin (HEP-TOS), which could self-assemble into nanoparticles in aqueous medium with paclitaxel (PTX) loaded in the core (Scheme 1). The chemical structure of the obtained polymer has been characterized by FT-IR, 1HNMR, suggesting the successful conjugation. At different feed ratio, polymers with different degree of substitution (DS) were prepared. The critical aggregation concentration ranged from 0.054 to 0.040 mg/mL with the increase of DS. Using a sonication method, HEP-TOS self-assembled nanoparticles were obtained with an average diameter of less than 180 nm and zeta potential of around −15 mV. PTXloaded HEP-TOS nanoparticles have been prepared via the dialysis method with a high drug loading efficiency (11.12%). Compared with PTX solution, the in vitro release of PTX from HEP-TOS nanoparticles exhibited significant sustained behavior without initial burst. In vitro cytotoxicity in MCF-7 and HepG2 cells proved both the safety of the carrier material and the effectiveness of PTX-loaded nanoparticles. The results above indicated the potential of HEP-TOS self-assembled nanoparticles for targeted delivery of PTX to tumor tissues.
Scheme 1. Preparation of PTX-loaded HEP-TOS self-assembled nanoparticles.
This work is supported by the Natural Science Foundation of Shandong Province, China (No. ZR2011HM026) and the National Natural Science Foundation of China (No. 30973646).
http://dx.doi.org/10.1016/j.nano.2015.12.293
prostate cancer and leukemia, etc. Unfortunately, the clinical application of PS has been hampered due to its poor water-solubility and relatively short half-life. To overcome the hurdle, the self-assembled nanoparticles based on eightarm-polyethylene glycol–pterostilbene (8arm-PEG-PS) conjugates were first presented. The 8arm-PEG-PS conjugates were synthesized by anesterification reaction between the carboxyl group of 8arm-polyethylene glycol and the hydroxyl group of PS. Then, they self-assembled into nanoparticles (Figure 1) to improve their pharmacological profiles. The nanoparticles have a small size (~ 100 nm) and exhibited significantly high water solubility and excellent in vitro anticancer activity compared with free PS. In vivo study demonstrated the superior therapeutic effect of nanoparticles on inhibition of tumor growth with lower systemic toxicity. On the basis of these results, we believe that the8arm-PEG-PS nanoparticles have great promise toward cancer therapy.
551
Figure 1. The synthesis of the amphiphilic phospholipid-mimicking prodrugs (a). Illustration of mPEG-Diosgenin nanoparticles encapsulated DHA for codelivery (b). TEM images of mPEG-Diosgenin encapsulate DHA nanoparticles. Inset: single nanoparticle TEM image at higher resolution (c). http://dx.doi.org/10.1016/j.nano.2015.12.292
Self-assembled nanoparticles based on α-tocopherol succinate-modified heparin for targeted delivery of paclitaxel Xiaoye Yang, Guangxi Zhai⁎, Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, China ⁎Corresponding author. E-mail address: [email protected] (G. Zhai)
Figure 1. Synthesis of eight-arm-polyethylene glycol-PS. TEM of nanoparticles.
http://dx.doi.org/10.1016/j.nano.2015.12.291
Self-assembled nanoparticles based on poly(ethylene glycol)-diosgenin prodrugs for co-delivery of anticancer drugs Chunxiao Li, Lin Dai, Kefeng Liu, Jiandu Lei⁎, Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing, P.R. China ⁎Corresponding author. E-mail address: [email protected] (J. Lei) Diosgenin is a steroidal saponin from a therapeutic herb, fenugreek. It is reported to be an important steroidal metabolite used as a starting material for the synthesis of antitumor drugs, as it exhibits estrogenic activity. Recently, a series of preclinical and mechanistic studies have shown great potential of diosgenin in the therapy for cancer. However, clinical application of diosgenin in cancer therapy is limited due to undesirable pharmaceutical characteristics such as its consequently poor solubility, relatively short half-life, and low bioavailability. In this study, we proposed to synthesize an amphiphilic phospholipidmimicking prodrugs system mPEG-Diosgenin by using methoxy poly(ethylene glycol). The prodrugs formed stable liposome-like nanoparticles with a high diosgenin loading content and no burst release in aqueous solution. In addition, they can be used as nanocarriers for co-delivery of another anticancer drug dihydroartemisinin (DHA) by a simple nanoprecipitation method. The obtained nanoparticles possessed appropriate size, high drug loading efficiency of diosgenin and DHA, slowly release drugs, higher the blood circulation half-time, and high synergistic effects. Hence, the mPEG-Diosgenin nanoparticle is a promising drug delivery system for cancer therapy.
To realize the efficient delivery of chemotherapeutic agents to tumor sites, numerous advanced vehicles have been investigated. Among them, self-assembled nanoparticles based on amphiphilic polymers have gained considerable interest. In this study, heparin was utilized as the hydrophilic backbone in view of its unique biological and physiochemical characterizations, especially the anti-angiogenesis and anti-metastasis activities. α-Tocopherol succinate was grafted to the backbone via coupling reaction, producing a novel amphiphilic polymer, α-tocopherol succinate modified heparin (HEP-TOS), which could self-assemble into nanoparticles in aqueous medium with paclitaxel (PTX) loaded in the core (Scheme 1). The chemical structure of the obtained polymer has been characterized by FT-IR, 1HNMR, suggesting the successful conjugation. At different feed ratio, polymers with different degree of substitution (DS) were prepared. The critical aggregation concentration ranged from 0.054 to 0.040 mg/mL with the increase of DS. Using a sonication method, HEP-TOS self-assembled nanoparticles were obtained with an average diameter of less than 180 nm and zeta potential of around −15 mV. PTXloaded HEP-TOS nanoparticles have been prepared via the dialysis method with a high drug loading efficiency (11.12%). Compared with PTX solution, the in vitro release of PTX from HEP-TOS nanoparticles exhibited significant sustained behavior without initial burst. In vitro cytotoxicity in MCF-7 and HepG2 cells proved both the safety of the carrier material and the effectiveness of PTX-loaded nanoparticles. The results above indicated the potential of HEP-TOS self-assembled nanoparticles for targeted delivery of PTX to tumor tissues.
Scheme 1. Preparation of PTX-loaded HEP-TOS self-assembled nanoparticles.
This work is supported by the Natural Science Foundation of Shandong Province, China (No. ZR2011HM026) and the National Natural Science Foundation of China (No. 30973646).
http://dx.doi.org/10.1016/j.nano.2015.12.293