Synthesis of a Novel Polyfunctional Anionic Macroinitiator from a Polyfunctional 1,1‐Diphenylethylene Agent

Cheng, Chong; Yang, Nan‐Loh

doi:10.1002/marc.200500349

Cited by 13 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BPDC 6 showed a monomodal GPC peak (curve f, Figure ), corresponding to a M n of 68.7 kDa and a PDI of 1.16 relative to linear polystyrenes. Its M n GPC was smaller than its M n NMR , as a result of its densely grafted compact structure …”

Section: Resultsmentioning

confidence: 95%

See 1 more Smart Citation

Well-Defined Degradable Brush Polymer–Drug Conjugates for Sustained Delivery of Paclitaxel

et al. 2012

Self Cite

View full text Add to dashboard Cite

To achieve a conjugated drug delivery system with high drug loading but minimal long-term side effects, a degradable brush polymer-drug conjugate (BPDC) was synthesized through azide-alkyne click reaction of acetylene-functionalized polylactide (PLA) with azide-functionalized paclitaxel (PTXL) and poly(ethylene glycol) (PEG). Well-controlled structures of the resulting BPDC and its precursors were verified by (1)H NMR and gel permeation chromatography (GPC) characterizations. With nearly quantitative click efficiency, drug loading amount of the BPDC reached 23.2 wt %. Both dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM) imaging indicated that the BPDC had a nanoscopic size around 10-30 nm. The significant hydrolytic degradability of the PLA backbone of the BPDC was confirmed by GPC analysis of its incubated solution. Drug release study showed that PTXL moieties can be released through the cleavage of the hydrolyzable conjugation linkage in pH 7.4 at 37 °C, with 50% release in about 22 h. As illustrated by cytotoxicity study, while the polymeric scaffold of the BPDC is nontoxic, the BPDC exhibited higher therapeutic efficacy toward MCF-7 cancer cells than free PTXL at 0.1 and 1 μg/mL. Using Nile red as encapsulated fluorescence probe, cell uptake study showed effective internalization of the BPDC into the cells.

show abstract

Section: Resultsmentioning

confidence: 95%

“…Its M n GPC was smaller than its M n NMR , as a result of its densely grafted compact structure. 38 Due to the hydrophilicity of the grafted PEG chains of 6, the water solubility of 6 is excellent. It can be quickly dissolved in water without any external assistance to give aqueous solutions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Well-Defined Degradable Brush Polymer–Drug Conjugates for Sustained Delivery of Paclitaxel

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…By GPC analysis, 9 had a M n of 46.7 kDa and a PDI of 1.32 related to linear polystyrenes. Because 86 wt % of 9 was from precursor 8 , according to the large M n,GPC relative to M n,NMR for 8 , the small M n,GPC relative to M n,NMR for 9 indicated its compact macromolecular architecture due to grafting . By DLS analysis (Figure ), 9 showed hydrodynamic sizes of 8–40 nm, with volume-average hydrodynamic diameter ( D h,v ) of 18.4 nm, in water that is a selective solvent for PEG chains of 9 .…”

Section: Resultsmentioning

confidence: 99%

Functional Polylactide-g-Paclitaxel–Poly(ethylene glycol) by Azide–Alkyne Click Chemistry

et al. 2011

Self Cite

View full text Add to dashboard Cite

Functional polylactide-g-paclitaxel–poly(ethylene glycol), a novel graft polymer–drug conjugate (GPDC) with paclitaxel (PTXL) as the divalent agent to bridge between the degradable polylactide (PLA)-based backbone and hydrophilic poly(ethylene glycol) (PEG) side chains, were prepared by the copper-catalyzed azide–alkyne cycloaddition reaction of acetylene-functionalized polylactide (PLA) with azide-functionalized PTXL–PEG conjugate. The acetylene-functionalized PLA was prepared by ring-opening copolymerization (ROCP) of acetylene-functionalized LA monomer with l-lactide (LA). The azide-functionalized PTXL–PEG conjugate was prepared by multistep organic synthesis. The well-controlled chemical structures of the GPDC and its precursors were verified by 1H NMR and GPC characterizations. DLS analysis indicated that GPDC molecules assembled in water to form nanoparticles with sizes of 8–40 nm. GPC analysis of buffer solutions (pH = 5.5 and 7.4) of the GPDC suggested the occurrence of multiple hydrolysis reactions under the experimental conditions, which resulted in the release of PTXL moieties and the cleavage of PLA-based backbone.

show abstract

“…Then, preformed polymeric grafts are attached via their chainends to these functional groups (grafting onto) or, alternatively, a second polymerization is initiated from those functional groups (grafting from). Here, as well as above, the grafts are most often prepared by anionic polymerization techniques [17] or ATRP [18] while ROMP as well as ATRP has been reported for backbone polymerization. A one-pot procedure using ATRP for the grafts and ROMP for the backbone has also been reported recently.…”

Section: Introductionmentioning

confidence: 99%

An All‐ROMP Route to Graft Copolymers

Hilf¹,

Kilbinger²

2007

Macromol. Rapid Commun.

View full text Add to dashboard Cite

A new versatile synthesis strategy for macromonomers has been developed that uses the living ring‐opening metathesis polymerization (ROMP) with commercial Grubbs first generation ruthenium initiators. Homopolymers as well as diblock copolymers were end‐functionalized with norbornene derivatives to serve as macromonomers. The graft copolymerization of the macromonomers was also carried out employing ROMP. Well‐defined and highly functional graft copolymers are accessible by this new synthetic route.magnified image

show abstract

Synthesis of a Novel Polyfunctional Anionic Macroinitiator from a Polyfunctional 1,1‐Diphenylethylene Agent

Cited by 13 publications

References 18 publications

Well-Defined Degradable Brush Polymer–Drug Conjugates for Sustained Delivery of Paclitaxel

Well-Defined Degradable Brush Polymer–Drug Conjugates for Sustained Delivery of Paclitaxel

Functional Polylactide-g-Paclitaxel–Poly(ethylene glycol) by Azide–Alkyne Click Chemistry

An All‐ROMP Route to Graft Copolymers

Contact Info

Product

Resources

About