scholarly journals Formaldehyde-Doxorubicin Dual Polymeric Drug Delivery System for Higher Efficacy and Limited Cardiotoxicity of Anthracyclines

2020 ◽  
Author(s):  
Estela Ordonez ◽  
Laken Kendrick-Williams ◽  
EVA HARTH
Keyword(s):  
Delivery System ◽  
Raft Polymerization ◽  
Release Kinetics ◽  
Therapeutic Index ◽  
Ph Responsive ◽  
System Combination ◽  
Polymeric Drug Delivery ◽  
Reversible Addition ◽  
Tumor Environment ◽  
Polymeric Delivery

<p>We report the synthesis of a dual delivery system composed of a chemically bound pH-responsive formaldehyde polymer prodrug and pH-responsive doxorubicin loaded nanoparticles to increase the therapeutic index of anthracyclines by limiting the cardiotoxicity of doxocrubicin by working in synergy with formaldehyde to enable the formation of DOX-DNA adducts. Polyacrylates bearing 1,2- and 1,3- pendant diols were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization to conjugate formaldehyde, forming 5- or 6-membered acetal rings with tunable conjugation percentages (1.5 – 10 wt%) for controlled release in acidic environments of the tumor extracellular matrix. The formaldehyde-conjugated prodrugs are then combined with polyester nanoparticles formed by intermolecular crosslinking via oxime click chemistry of less than 200 nm in size containing 14 wt% encapsulated Doxorubicin (DOX). Release kinetics show a sustained release of both DOX and formaldehyde at pH 5.0, mimicking the low pH of the tumor environment whereas insignificant release was recorded at physiological pH. The cell viability of the dual delivery system combination was evaluated in 4 T1 breast cancer cells resulting in a considerably increase of cell death of about 4-fold compared to free DOX alone. The resulting polymeric delivery system is the first example reported of a DOX and formaldehyde co-administration, demonstrating the potential significant effect of formaldehyde for an improved anti-cancer efficacy of DOX and towards a reduced cardiotoxicity of DOX.</p>

scholarly journals Formaldehyde-Doxorubicin Dual Polymeric Drug Delivery System for Higher Efficacy and Limited Cardiotoxicity of Anthracyclines

2020 ◽  
Author(s):  
Estela Ordonez ◽  
Laken Kendrick-Williams ◽  
EVA HARTH
Keyword(s):  
Delivery System ◽  
Raft Polymerization ◽  
Release Kinetics ◽  
Therapeutic Index ◽  
Ph Responsive ◽  
System Combination ◽  
Polymeric Drug Delivery ◽  
Reversible Addition ◽  
Tumor Environment ◽  
Polymeric Delivery

<p>We report the synthesis of a dual delivery system composed of a chemically bound pH-responsive formaldehyde polymer prodrug and pH-responsive doxorubicin loaded nanoparticles to increase the therapeutic index of anthracyclines by limiting the cardiotoxicity of doxocrubicin by working in synergy with formaldehyde to enable the formation of DOX-DNA adducts. Polyacrylates bearing 1,2- and 1,3- pendant diols were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization to conjugate formaldehyde, forming 5- or 6-membered acetal rings with tunable conjugation percentages (1.5 – 10 wt%) for controlled release in acidic environments of the tumor extracellular matrix. The formaldehyde-conjugated prodrugs are then combined with polyester nanoparticles formed by intermolecular crosslinking via oxime click chemistry of less than 200 nm in size containing 14 wt% encapsulated Doxorubicin (DOX). Release kinetics show a sustained release of both DOX and formaldehyde at pH 5.0, mimicking the low pH of the tumor environment whereas insignificant release was recorded at physiological pH. The cell viability of the dual delivery system combination was evaluated in 4 T1 breast cancer cells resulting in a considerably increase of cell death of about 4-fold compared to free DOX alone. The resulting polymeric delivery system is the first example reported of a DOX and formaldehyde co-administration, demonstrating the potential significant effect of formaldehyde for an improved anti-cancer efficacy of DOX and towards a reduced cardiotoxicity of DOX.</p>

scholarly journals Photo-Responsive Polymersomes as Drug Delivery System for Potential Medical Applications

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5147
Author(s):  
Wanting Hou ◽  
Ruiqi Liu ◽  
Siwei Bi ◽  
Qian He ◽  
Haibo Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Block Copolymers ◽  
Drug Delivery System ◽  
Delivery System ◽  
Raft Polymerization ◽  
Amphiphilic Block Copolymers ◽  
Medical Applications ◽  
Drug Molecules ◽  
Reversible Addition ◽  
Raft Agent

Due to a strong retardation effect of o-nitrobenzyl ester on polymerization, it is still a great challenge to prepare amphiphilic block copolymers for polymersomes with a o-nitrobenzyl ester-based hydrophobic block. Herein, we present one such solution to prepare amphiphilic block copolymers with pure poly (o-nitrobenzyl acrylate) (PNBA) as the hydrophobic block and poly (N,N’-dimethylacrylamide) (PDMA) as the hydrophilic block using bulk reversible addition-fragmentation chain transfer (RAFT) polymerization of o-nitrobenzyl acrylate using a PDMA macro-RAFT agent. The developed amphiphilic block copolymers have a suitable hydrophobic/hydrophilic ratio and can self-assemble into photoresponsive polymersomes for co-loading hydrophobic and hydrophilic cargos into hydrophobic membranes and aqueous compartments of the polymersomes. The polymersomes demonstrate a clear photo-responsive characteristic. Exposure to light irradiation at 365 nm can trigger a photocleavage reaction of o-nitrobenzyl groups, which results in dissociation of the polymersomes with simultaneous co-release of hydrophilic and hydrophobic cargoes on demand. Therefore, these polymersomes have great potential as a smart drug delivery nanocarrier for controllable loading and releasing of hydrophilic and hydrophobic drug molecules. Moreover, taking advantage of the conditional releasing of hydrophilic and hydrophobic drugs, the drug delivery system has potential use in medical applications such as cancer therapy.

Development of Core-Crosslinked Micelles for Drug Delivery System

2012 ◽  
Vol 486 ◽  
pp. 449-454 ◽  
Author(s):  
Yue Zhao ◽  
Ming Tao Liang ◽  
Yoseop Kim ◽  
Xin Tan ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Raft Polymerization ◽  
Poly Ethylene Glycol ◽  
Reversible Addition ◽  
Self Assembled ◽  
Poly Ethylene ◽  
Crosslinked Micelles ◽  
Glycol Methyl Ether

A polymer drug delivery system was developed using crosslinked self-assembled micelles, which form stable coreshell particles. The block copolymer, composed of poly [poly (ethylene glycol) methyl ether methacrylat-block-[poly (methyl methacrylate-p-nitrophenyl acrylate)] [P(PEGMEMA)-b-P(MMA-NPA)], was synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization. The self-assembled micelles were stabilized by core crosslinking through the reaction of p-nitrophenyl acrylate with 1,8-octandiamine forming stable coreshell particles.

scholarly journals pH-Responsive Chiral Nanostructures

2011 ◽  
Vol 64 (8) ◽  
pp. 1041 ◽  
Author(s):  
Jianzhong Du ◽  
Helen Willcock ◽  
Nga Sze Ieong ◽  
Rachel K. O'Reilly
Keyword(s):  
Amino Acids ◽  
Chain Transfer ◽  
Raft Polymerization ◽  
Synthetic Polymers ◽  
Amphiphilic Block Copolymers ◽  
Current Interest ◽  
Ph Responsive ◽  
Block Polymers ◽  
Reversible Addition ◽  
Chiral Nanostructures

There is great current interest in the design of robust synthetic polymers for the preparation of novel functional, well-defined, biocompatible and tailorable materials for a range of possible applications. In this work we have used reversible addition fragmentation chain transfer (RAFT) polymerization to prepare chiral and responsive amphiphilic block copolymers (based on polyphenylalanine acrylamide), which can be assembled at different pHs to form well-defined nanostructures. The morphology and size of the derived block polymers were explored using TEM, DLS and SLS measurements, while stability was examined by fluorescence and NMR spectroscopy. The application of these chiral and responsive nanostructures in the resolution of hydrophilic racemic amino acids has also been explored.

Synthesis of pH-Responsive Glycopolymer with End Group Zinc(II) Phthalocyanines as Potential Photosensitizer

2020 ◽  
Vol 996 ◽  
pp. 82-87
Author(s):  
Shu Guo Dong ◽  
Gui Hua Cui ◽  
Qian Duan
Keyword(s):  
Photodynamic Therapy ◽  
Singlet Oxygen ◽  
Raft Polymerization ◽  
Photophysical Properties ◽  
Water Soluble ◽  
Quantum Yields ◽  
Oxygen Species ◽  
Ph Responsive ◽  
Reversible Addition ◽  
Singlet Oxygen Species

A novel end-functionalized glycopolymer poly (3-O-methacryloyl-D-glucofuranose) -b-poly (2-Diethylaminoethyl Methacrylate) (PMAGlc-b-PDEA-ZnTAPc) with zinc (II) teraamaninophthalocyanine was synthesized. First, a pH-responsive copolymer PMAIpG-b-PDEA was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Then PMAIpG-b-PDEA reacted with ZnTAPc and deprotected to form a water-soluble and pH-responsive photosensitizer. The structure of the PMAGlc-b-PDEA-ZnTAPc was characterized by 1H NMR and GPC. The photophysical properties were evaluated by UV-Vis and fluorescence spectra. The PMAGlc-b-PDEA-ZnTAPc can generate singlet oxygen species with good singlet oxygen quantum yields (Φ△=0.38), which is believed to be the major cytotoxic reactive oxygen species (ROS) for photodynamic therapy. The ZnPc functionalized glycopolymer will be used as a potential photosensitizer in the fields of photodynamic therapy.

Using RAFT Polymerization to Synthesize Potential Drug/Gene Delivery System

2012 ◽  
Vol 535-537 ◽  
pp. 1079-1082
Author(s):  
Yue Zhao ◽  
Xin Tan ◽  
Ling Zhang
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Chain Transfer ◽  
Raft Polymerization ◽  
Potential Drug ◽  
Gene Delivery System ◽  
Cationic Micelles ◽  
Reversible Addition ◽  
Raft Agent

Biodegradable cationic micelles were prepared from P(PEGMEMA)-PDMAEMA-PCL-PDMAEMA-P(PEGMEMA) five blocks copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization with CPADB-PCL-CPADB (CPADB: 4-Cyanopentanoic acid dithiobenzoate; PCL: 5600 Da) as a macro-RAFT agent. These five blocks copolymers formed nano-sized micelles in water.

scholarly journals pH and redox dual-sensitive drug delivery system constructed based on fluorescent carbon dots

RSC Advances ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 2656-2663
Author(s):  
Boye Zhang ◽  
Qianqian Duan ◽  
Yi Li ◽  
Jianming Wang ◽  
Wendong Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Cancer Cells ◽  
Fluorescence Imaging ◽  
Drug Delivery System ◽  
Delivery System ◽  
Carbon Dots ◽  
Ph Responsive ◽  
Charge Reversal ◽  
Fluorescent Carbon Dots

The system is pH-responsive and redox-controlled release. And the charge reversal and size transitions of the system can enhance the targeted ability. Moreover, the system can recognize the cancer cells by the fluorescence imaging.

Self-Healing Hydrophobic POSS-functionalized Fluorinated Copolymer via RAFT Polymerization and dynamic Diels-Alder Reaction

2021 ◽  
Author(s):  
Siva Ponnupandian ◽  
Prantik Mondal ◽  
Thomas Becker ◽  
Richard Hoogenboom ◽  
Andrew B Lowe ◽  
...  
Keyword(s):  
Chain Transfer ◽  
Raft Polymerization ◽  
Alder Reaction ◽  
Diels Alder ◽  
Self Healing ◽  
Diels Alder Reaction ◽  
Reversible Addition

This investigation reports the preparation of a tailor-made copolymer of furfuryl methacrylate (FMA) and trifluoroethyl methacrylate (TFEMA) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The furfuryl groups of the copolymer...

scholarly journals Nano-Assemblies from Amphiphilic PnBA-b-POEGA Copolymers as Drug Nanocarriers

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1164
Author(s):  
Angeliki Chroni ◽  
Thomas Mavromoustakos ◽  
Stergios Pispas
Keyword(s):  
Molecular Weight ◽  
Chain Transfer ◽  
Raft Polymerization ◽  
Polymeric Nanocarriers ◽  
Reversible Addition ◽  
2D Noesy ◽  
Drug Nanocarriers ◽  
Glycol Methyl Ether ◽  
Different Molecular Weight

The focus of this study is the development of highly stable losartan potassium (LSR) polymeric nanocarriers. Two novel amphiphilic poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) copolymers with different molecular weight (Mw) of PnBA are synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, followed by the encapsulation of LSR into both PnBA-b-POEGA micelles. Based on dynamic light scattering (DLS), the PnBA30-b-POEGA70 and PnBA27-b-POEGA73 (where the subscripts denote wt.% composition of the components) copolymers formed micelles of 10 nm and 24 nm in water. The LSR-loaded PnBA-b-POEGA nanocarriers presented increased size and greater mass nanostructures compared to empty micelles, implying the successful loading of LSR into the inner hydrophobic domains. A thorough NMR (nuclear magnetic resonance) characterization of the LSR-loaded PnBA-b-POEGA nanocarriers was conducted. Strong intermolecular interactions between the biphenyl ring and the butyl chain of LSR with the methylene signals of PnBA were evidenced by 2D-NOESY experiments. The highest hydrophobicity of the PnBA27-b-POEGA73 micelles contributed to an efficient encapsulation of LSR into the micelles exhibiting a greater value of %EE compared to PnBA30-b-POEGA70 + 50% LSR nanocarriers. Ultrasound release profiles of LSR signified that a great amount of the encapsulated LSR is strongly attached to both PnBA30-b-POEGA70 and PnBA27-b-POEGA73 micelles.

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