scholarly journals Development of Self-Associating SN-38-Conjugated Poly(ethylene oxide)-Poly(ester) Micelles for Colorectal Cancer Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1033
Author(s):  
Sams M. A. Sadat ◽  
Mohammad Reza Vakili ◽  
Igor M. Paiva ◽  
Michael Weinfeld ◽  
Afsaneh Lavasanifar
Keyword(s):  
Colorectal Cancer ◽  
Ethylene Oxide ◽  
Water Solubility ◽  
In Vitro Release ◽  
Critical Micellar Concentration ◽  
Anticancer Activities ◽  
Poly Ethylene Oxide ◽  
Self Assembled ◽  
Poly Ethylene

The clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38), which is the active metabolite of irinotecan, has been hampered because of its practical water-insolubility. In this study, we successfully synthesized two self-associating SN-38-polymer drug conjugates to improve the water-solubility of SN-38, while retaining its anticancer activity. The polymeric micellar SN-38 conjugates were composed of either methoxy-poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) conjugated to SN-38 at the PBCL end (mPEO-b-PBCL/SN-38) or mPEO-block-poly(α-carboxyl-ε-caprolactone) attached to SN-38 from the pendent-free carboxyl site (mPEO-b-PCCL/SN-38). The chemical structure of block copolymers was confirmed by 1H NMR. The physicochemical characterizations of their self-assembled structures including size, surface charge, polydispersity, critical micellar concentration, conjugation content and efficiency, morphology, kinetic stability, and in vitro release of SN-38 were compared between the two formulations. In vitro anticancer activities were evaluated by measuring cellular cytotoxicity and caspase activation by MTS and Caspase-Glo 3/7 assays, respectively. The hemolytic activity of both micellar structures against rat red blood cells was also measured. The results showed the formation of SN-38-polymeric micellar conjugates at diameters < 50 nm with a narrow size distribution and sustained release of SN-38 for both structures. The loading content of SN-38 in mPEO-b-PBCL and mPEO-b-PCCL were 11.47 ± 0.10 and 12.03 ± 0.17 (% w/w), respectively. The mPEO-b-PBCL/SN-38, end-capped micelles were kinetically more stable than mPEO-b-PCCL/SN-38. The self-assembled mPEO-b-PBCL/SN-38 and mPEO-b-PCCL/SN-38 micelles resulted in significantly higher cytotoxic effects than irinotecan against human colorectal cancer cell lines HCT116, HT-29, and SW20. The CRC cells were found to be 70-fold to 330-fold more sensitive to micellar SN-38 than irinotecan, on average. Both SN-38-incorporated micelles showed two-fold higher caspase-3/7 activation levels than irinotecan. The mPEO-b-PBCL/SN-38 micelles were not hemolytic, but mPEO-b-PCCL/SN-38 showed some hemolysis. The overall results from this study uphold mPEO-b-PBCL/SN-38 over mPEO-b-PCCL/SN-38 micellar formulation as an effective delivery system of SN-38 that warrants further preclinical investigation.

Fabrication of electrospun poly(ethylene oxide)–poly(capro lactone) composite nanofibers for co-delivery of niclosamide and silver nanoparticles exhibits enhanced anti-cancer effects in vitro

2016 ◽  
Vol 4 (4) ◽  
pp. 726-742 ◽  
Author(s):  
Poornima Dubey ◽  
P. Gopinath
Keyword(s):  
Silver Nanoparticles ◽  
Ethylene Oxide ◽  
Anticancer Drugs ◽  
Composite Nanofibers ◽  
Water Solubility ◽  
Intrinsic Property ◽  
Anti Cancer ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

An intrinsic property of many anticancer drugs including niclosamide is poor water solubility, which hindered their translation from laboratory to clinics.

Thermosensitive In Situ Gel Containing Luteolin Micelles is a Promising Efficient Agent for Colorectal Cancer Peritoneal Metastasis Treatment

2020 ◽  
Vol 16 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Yuzhu Hu ◽  
Xiaoye Chen ◽  
Zongyuan Li ◽  
Songping Zheng ◽  
Yongzhong Cheng
Keyword(s):  
Colorectal Cancer ◽  
Drug Release ◽  
Peritoneal Metastasis ◽  
Water Solubility ◽  
Local Therapy ◽  
Cancer Drug ◽  
Poly Ethylene ◽  
Vegetables And Fruits

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.

Surface Modification of Copolyether-Urethane Catheters with Poly(Ethylene Oxide)

1989 ◽  
Vol 12 (6) ◽  
pp. 390-394 ◽  
Author(s):  
E. Brinkman ◽  
A. Poot ◽  
T. Beugeling ◽  
L. Van Der Does ◽  
A. Bantjes
Keyword(s):  
Surface Modification ◽  
Ethylene Oxide ◽  
Blood Compatibility ◽  
Angle Measurements ◽  
Fold Reduction ◽  
Contact Angle Measurements ◽  
Platelet Deposition ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

Pellethane 2363 80A catheters were modified with poly(ethylene oxide) in order to improve their blood compatibility. Contact angle measurements showed that Pellethane 2363 80A surfaces had increased wettability after this modification. The results of in vitro blood compatibility tests showed that surface modification with poly(ethylene oxide) resulted in a five-fold reduction of platelet deposition. Activation of coagulation was not affected.

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