Well-Defined Diblock Poly(ethylene glycol)-b-Poly(ε-caprolactone)-Based Polymer-Drug Conjugate Micelles for pH-Responsive Delivery of Doxorubicin

Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC micelles, revealed their improved anticancer efficiency towards MCF-7 cells as compared to free DOX.

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Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

Toxicologic Pathology ◽

10.1177/0192623318810199 ◽

2018 ◽

Vol 47 (3) ◽

pp. 426-432 ◽

Cited By ~ 3

Author(s):

Sivan Yogev ◽

Ayelet Shabtay-Orbach ◽

Abraham Nyska ◽

Boaz Mizrahi

Keyword(s):

Block Copolymer ◽

Ethylene Glycol ◽

Medical Devices ◽

Poly Lactic Acid ◽

Poly Ethylene Glycol ◽

Thermoresponsive Polymers ◽

Wide Range ◽

Poly Ethylene

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

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A Tunable pH-Responsive Nanomaterials for Cancer Delivery

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.750-752.1476 ◽

2013 ◽

Vol 750-752 ◽

pp. 1476-1479 ◽

Cited By ~ 1

Author(s):

Bin Liu ◽

Guan Hui Gao ◽

Peng Liu ◽

Hu Qiang Yi ◽

Wei Wei ◽

...

Keyword(s):

Drug Delivery ◽

Ethylene Glycol ◽

Potential Application ◽

Ph Responsive ◽

Poly Ethylene Glycol ◽

Positive Potential ◽

Ph Values ◽

Drugs In Blood ◽

Poly Ethylene

In this paper, we successfully designed a pH-responsive micelles based on hybrid polypeptide copolymers of poly (L-lysine-4-Azepan-1-yl-butyric)-b-poly (ethylene glycol)-b-poly (L-lysine-Diisopropylamide)-b-poly (L-leucine) (PLL(A)-PEG-PLL(B)-PLLeu) for efficient drug delivery. This pH-responsive nanoparticles were able to response to different pH values (pH=6.8 and 5.5). In vitro, these nanoparticles exhibited a stable and evenly distributed approximately 51 nm, a slightly positive potential about 10.3 mv at pH 7.4, which were crucial for the circulation of drugs in blood. While size and potential were about 130 nm and 34.7 mv at pH 6.8, which were good for drugs in membrane. Furthermore, the loading capability of DOX was up to 11.3%, and the pH-responsive release efficiency reached to 68.3% at pH 5.5. The results indicated that these micelles had huge potential application in cancer delivery.

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