Synthesis of Polyester Nanoparticles in Miniemulsion Obtained by Radical Ring‐Opening of BMDO and Their Potential as Biodegradable Drug Carriers

Siebert, Joerg Max; Baumann, Daniela; Zeller, Anke; Mailänder, Volker; Landfester, Katharina

doi:10.1002/mabi.201100236

Cited by 32 publications

(39 citation statements)

References 33 publications

(29 reference statements)

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“…BMDO was synthesized following literature procedures 36,37 , taking extra precaution to prevent hydrolysis of the product. All glassware was oven-dried overnight.…”

Section: Methodsmentioning

confidence: 99%

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Decker

Maynard

2015

European Polymer Journal

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Poly(ethylene glycol) (PEG)-protein therapeutics exhibit enhanced pharmacokinetics, but have drawbacks including decreased protein activities and polymer accumulation in the body. Therefore a major aim for second-generation polymer therapeutics is to introduce degradability into the backbone. Herein we describe the synthesis of poly(poly(ethylene glycol methyl ether methacrylate)) (pPEGMA) degradable polymers with protein-reactive end-groups via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the subsequent covalent attachment to lysozyme through a reducible disulfide linkage. RAFT copolymerization of cyclic ketene acetal (CKA) monomer 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) with PEGMA yielded two polymers with number-average molecular weight (Mn) (GPC) of 10.9 and 20.9 kDa and molecular weight dispersities (Ð) of 1.34 and 1.71, respectively. Hydrolytic degradation of the polymers was analyzed by 1H-NMR and GPC under basic and acidic conditions. The reversible covalent attachment of these polymers to lysozyme, as well as the hydrolytic and reductive cleavage of the polymer from the protein, was analyzed by gel electrophoresis and mass spectrometry. Following reductive cleavage of the polymer, an increase in activity was observed for both conjugates, with the released protein having full activity. This represents a method to prepare PEGylated proteins, where the polymer is readily cleaved from the protein and the main chain of the polymer is degradable.

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“…BMDO was synthesized following literature procedures 36,37 , taking extra precaution to prevent hydrolysis of the product. All glassware was oven-dried overnight.…”

Section: Methodsmentioning

confidence: 99%

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Decker

Maynard

2015

European Polymer Journal

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“…Nanoparticles (NPs) are widely used as a matrix for the conjugation of drug molecules as well as for encapsulation, which protects the drugs, controls their biodistribution, and allows for their release in a sustained and/or in a trigger‐responsive manner. [ 6–9 ] In addition, the size of NPs endows them with the advantage of enhanced permeability and retention effect, which can improve the passive target of NPs to the target tumor site. [ 10 ] Our group has focused on CA4‐polymer‐conjugate NPs for enhanced antitumor therapy over the past 5 years.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles Composed of PEGylated Alternating Copolymer‐Combretastatin A4 Conjugate for Cancer Therapy

Zhang

Liu

Wang

et al. 2021

Macromolecular Bioscience

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Chemotherapy using vascular targeting agents is an emerging new approach for cancer therapy. Combretastatin A4 (CA4) is a leading vascular‐disrupting agent that targets the tumor blood vasculature for clinical tumor elimination. However, the extremely poor water solubility of CA4 hinders its biomedical applications. In this study, nanoparticles composed of novel PEGylated alternating copolymer‐CA4 conjugates are designed to improve the therapeutic efficiency of CA4. First, an alternating copolymer with an alkene‐pendant is synthesized by mPEG‐OH‐initiated ring‐opening copolymerization. Then, side carboxyl groups are introduced by a thio‐ene “click” chemical reaction, followed with CA4 conjugation through the Yamaguchi‐reaction, resulting in the target copolymer, mPEG‐b‐P(PA‐alt‐GCA4). Interestingly, the polymer‐drug conjugates can self‐assemble into nanoparticles with an average diameter of 55.6 nm. The in vitro drug release and cytotoxicity of the obtained CA4‐NPs toward 4T1 cells are investigated. Finally, the antitumor efficiency is evaluated in a 4T1‐tumor bearing murine model. The in vivo test results demonstrate that CA4‐NPs inhibited tumor growth much more efficiently at doses of 30 and 60 mg kg−1, compared with the control group.

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“…While in principle being a highly interesting process, RROP did not gain much interest and remained largely unused for a long time, mostly due to the seemingly better accessibility of polyesters from either step‐growth polymerization or the ring‐opening polymerization of lactones . However, in recent years RROP has seen a revival and a considerable amount of studies have been published on polyester materials stemming from this process . This resurrection is mostly due to two factors, (i) being the availability of controlled radical polymerization (CRP) methods that allow (in combination with CKAs) for the simple design of mixed polyester/polyvinyl (block) copolymers with controlled structure, functionality, and defined dispersity and (ii) the general possibility to produce statistical copolymers of CKAs with conventional vinyl monomers that allow for the synthesis of materials that feature the degradability of the polyester component…”

Section: Introductionmentioning

confidence: 99%

“…2,3 However, in recent years RROP has seen a revival and a considerable amount of studies have been published on polyester materials stemming from this process. [4][5][6][7][8][9] This resurrection is mostly due to two factors, (i) being the availability of controlled radical polymerization (CRP) methods [10][11][12] that allow (in combination with CKAs) for the simple design of mixed polyester/polyvinyl (block) copolymers with controlled structure, functionality, and defined dispersity and (ii) the general possibility to produce statistical copolymers of CKAs with conventional vinyl monomers that allow for the synthesis of materials that feature the degradability of the polyester component. 13 Especially the second feature is highly attractive for the design of materials for a broad range of applications.…”

mentioning

confidence: 99%

Synthesis of degradable poly(methyl methacrylate) star polymers via RAFT copolymerization with cyclic ketene acetals

Kobben

Ethirajan

Junkers

2014

J. Polym. Sci. Part A: Polym. Chem.

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Copolymerization of the cyclic ketene acetal 5,6benzo-2-methylene-1,3-dioxepane (BMDO) with methyl methacrylate (MMA) is studied with respect to its copolymerization parameters and the suitability to control BMDO/MMA copolymerizations via the reversible addition-fragmentation chain transfer (RAFT) technique to obtain linear and 4-arm star polymers. BMDO shows disparate copolymerization behavior with MMA and r 1 5 0.33 6 0.06 and r 2 5 6.0 6 0.8 have been determined for polymerization at 110 C in anisole from fitting copolymer composition vs. comonomer feed data to the Lewis-Mayo equation. Copolymerization of the two monomers is successful in RAFT polymerization employing a trithiocarbonate control agent. As desired, polymers contain only little amount of polyester units stemming from BMDO units and preliminary degradation experiment show that the polymer degrades slowly, but steadily in aqueous 1 M NaOH dispersion. Within ten days, the polymers are broken down to low molecular weight segments from an initial molecular weight of M n 5 6000 g mol 21 . Star (co)polymerization with an erythritolbased tetra-functional RAFT agent following the Z-group approach proceeds efficiently and polymers with a numberaverage molecular weight of 10,000 g mol 21 are readily obtained that degrade in similar manner as the linear copolymer counterparts.

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Synthesis of Polyester Nanoparticles in Miniemulsion Obtained by Radical Ring‐Opening of BMDO and Their Potential as Biodegradable Drug Carriers

Cited by 32 publications

References 33 publications

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Degradable PEGylated protein conjugates utilizing RAFT polymerization

Nanoparticles Composed of PEGylated Alternating Copolymer‐Combretastatin A4 Conjugate for Cancer Therapy

Synthesis of degradable poly(methyl methacrylate) star polymers via RAFT copolymerization with cyclic ketene acetals

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