Engineering thermoresponsive polymeric nanoshells

Cohn, Daniel; Sagiv, Hagit; Benyamin, Alexandra; Lando, Gilad

doi:10.1016/j.biomaterials.2009.02.026

Cited by 28 publications

(13 citation statements)

References 32 publications

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“…Cohn et al utilized the formation of micelles above the LCST of PEG-b-PPG-b-PEG triblock copolymers, where PPG was the hydrophobic poly(propylene glycol) block, also called poly(propylene oxide) (PPO), to form functional nanoshells, Figure 7 [116], by incorporating a methacrylate group onto each end of the block copolymers and crosslinking them while in a micellar configuration a collapsible and expandable shell structure was formed with an extremely large void spaces capable of encapsulating numerous moieties [116]. …”

Section: Cross Linked Micellesmentioning

confidence: 99%

Thermoresponsive Polymers for Biomedical Applications

2011

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Thermoresponsive polymers are a class of "smart" materials that have the ability to respond to a change in temperature; a property that makes them useful materials in a wide range of applications and consequently attracts much scientific interest. This review focuses mainly on the studies published over the last 10 years on the synthesis and use of thermoresponsive polymers for biomedical applications including drug delivery, tissue engineering and gene delivery. A summary of the main applications is given following the different studies on thermoresponsive polymers which are categorized based on their 3-dimensional structure; hydrogels, interpenetrating networks, micelles, crosslinked micelles, polymersomes, films and particles.

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Section: Cross Linked Micellesmentioning

confidence: 99%

Thermoresponsive Polymers for Biomedical Applications

2011

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“…Following the pioneering work by Wooley and co-workers, there has been increasing interest in utilizing the cross-linking approach to improve the stability of polymeric micelles for drug delivery [10, 13–22]. Thus far, the reported approaches include shell-cross-linking [13, 19–21, 23–25], core-cross-linking [10, 15–17] and cross-linking at the core-shell interface [18, 26].…”

Section: Introductionmentioning

confidence: 99%

Well-defined, reversible disulfide cross-linked micelles for on-demand paclitaxel delivery

et al. 2011

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To minimize premature release of drugs from their carriers during circulation in the blood stream, we have recently developed reversible disulfide cross-linked micelles (DCMs) that can be triggered to release drug at the tumor site or in cancer cells. We designed and synthesized thiolated linear-dendritic polymers (telodendrimers) by introducing cysteines to the dendritic oligo-lysine backbone of our previously reported telodendrimers comprised of linear polyethylene glycol (PEG) and a dendritic cluster of cholic acids. Reversibly cross-linked micelles were then prepared by the oxidization of thiol groups to disulfide bond in the core of micelles after the self-assembly of thiolated telodendrimers. The DCMs were spherical with a uniform size of 28 nm, and were able to load paclitaxel (PTX) in the core with superior loading capacity up to 35.5% (w/w, drug/micelle). Cross-linking of the micelles within the core reduced their apparent critical micelle concentration and greatly enhanced their stability in non-reductive physiological conditions as well as severe micelle-disrupting conditions. The release of PTX from the DCMs was significantly slower than that from non-cross-linked micelles (NCMs), but can be gradually facilitated by increasing the concentration of reducing agent (glutathione) to an intracellular reductive level. The DCMs demonstrated a longer in vivo blood circulation time, less hemolytic activities, and superior toxicity profiles in nude mice, when compared to NCMs. DCMs were found to be able to preferentially accumulate at the tumor site in nude mice bearing SKOV-3 ovarian cancer xenograft. We also demonstrated that the disulfide cross-linked micellar formulation of PTX (PTX-DCMs) was more efficacious than both free drug and the non-cross-linked formulation of PTX at equivalent doses of PTX in the ovarian cancer xenograft mouse model. The anti-tumor effect of PTX-DCMs can be further enhanced by triggering the release of PTX on-demand by the administration of the FDA approved reducing agent, N-acetylcysteine, after PTX-DCMs have reached the tumor site.

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“…Among various copolymers, the amphiphilic diblock copolymers composing of aliphatic polyesters such as poly(-caprolactone) (PCL) [24], poly(d,l-lactide) (PLA) [25,26], poly(glycolide) (PGA) and their copolymer poly(lactide-co-glycolide) (PLGA) [27] as hydrophobic segments and polyether such as PEG and pluronics [28][29][30] as hydrophilic segments, have been widely studied. Amphiphilic PEG-PCL block copolymers have been investigated in the morphologies, thermo-responsive hydrogels and drug delivery [31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%