Effect of molecular weight of PGG–paclitaxel conjugates on in vitro and in vivo efficacy

Yang, Danbo; Liu, Xiaoqing; Jiang, Xinguo; Liu, Yun; Ying, Wenbin; Wang, Hai; Bai, Hao; Taylor, Wayne E.; Wang, Yuwei; Clamme, Jean‐Pierre; Co, Erick W.; Chivukula, Padmanabh; Tsang, Kwok Yin; Jin, Y.; Yu, Lei

doi:10.1016/j.jconrel.2012.04.010

Cited by 43 publications

(49 citation statements)

References 31 publications

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“…The phenomenon where the cytotoxicity of free paclitaxel remains lower than the cytotoxicity of the drug-loaded micelles in 2D monolayer experiments has been previously observed 30,31,50,54 . In all these cases, the IC 50 value of free paclitaxel on the cancer cell line of interest was already extremely low with IC 50 values often being less than 10 nM.…”

Section: Cytotoxicity In 2d Monolayer Cell Culturementioning

confidence: 70%

“…In all likelihood, conjugation past this point is limited due to the steric hindrance caused by the paclitaxel units already attached to the polymer backbone. Use of carbodiimide reagents for the conjugation of paclitaxel to polymer chains have resulted in varying conjugation efficiencies of 60.8 -87.5% 17,23,30,31,50 . However, carbodiimide reactions often require anhydrous and/or inert conditions and an excess of coupling reagents and/or paclitaxel itself.…”

Section: Conjugation Of Ptx To Poegmea-b-pceamentioning

confidence: 99%

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Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel–Conjugate Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D Models

Stenzel

2015

Biomacromolecules

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The 2D monolayer cell culture model is often the first step in the prediction of the success or failure of a nanoparticle-based drug delivery system. However, there is often poor translation between the 2D monolayer in vitro results and the nanoparticle-drug performance in vivo. One possible way of bridging this gap is the use of multicellular tumor spheroids (MCTSs) as an intermediate in vitro model due to its 3D structure. This paper aims to quantify and compare the results obtained from traditional 2D monolayer cell cultures and 3D MCTS by studying the cytotoxic effects of free paclitaxel (PTX) and paclitaxel, which has been conjugated to a poly(ethylene glycol methyl ether acrylate)-b-poly(carboxyethyl acrylate) (POEGMEA-b-PCEA-PTX) block copolymer and self-assembled to give a micellar delivery system. The core of the micelle was cross-linked with a diamino nondegradable cross-linker to compare the effects of micelle stability on the results. Although the 2D prostate tumor cell culture results indicated that all micellar variants (IC50: 193-271 nM) were significantly less toxic than free paclitaxel (IC50: 15.2 nM), the micelles showed faster and higher cytotoxicity than free PTX in the 3D prostate MCTS. The cross-linking of micelles even showed accelerated antitumor activities to the MCTS compared with un-cross-linked micelles. The results indicate that DAO-cross-linked POEGMEA-b-PCEA-PTX conjugate micelles will be a useful nanodrug carrier for prostate cancer therapy. MCTS offers a very promising method of incorporating 3D structures into in vitro testing.

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Section: Cytotoxicity In 2d Monolayer Cell Culturementioning

confidence: 70%

Section: Conjugation Of Ptx To Poegmea-b-pceamentioning

confidence: 99%

Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel–Conjugate Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D Models

Stenzel

2015

Biomacromolecules

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“…The body weight of the mice was also recorded every other day for 1 week following drug administration. The MTD was determined to be the dose that induced ∼10% loss in body weight with no lethality and no notable behavior differences were noted [15]. The animals showing weight loss exceeding 20% were sacrificed, as changes of this magnitude often indicate lethal toxicity [16].…”

Section: In Vivo Mtd Studiesmentioning

confidence: 99%

Polymeric complex micelles with double drug-loading strategies for folate-mediated paclitaxel delivery

Liu

Feng

et al. 2015

Colloids and Surfaces B: Biointerfaces

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“…This approach enhances drug solubility, prolongs in vivo circulation, and reduces hostile effects, the last feature being of vital importance in various chemotherapy treatments. In this analysis of polymeric prodrug, is to link hydrophobic drug (curcumin) to a preformed hydrophilic polymer (PMMA-AA) as previous reports [7][8][9][10] to give complete water-soluble bioconjugate, moreover, some of the previously stated limitations of nanomaterials might mitigated by utilizing this approach [5].…”

Section: Introductionmentioning

confidence: 99%

pH Triggered Curcumin Release from PMMA-AA Coated ZnO Nanoparticles for Excellent Anti-Gastric Cancer Therapy

Dhivya¹,

Ranjani²,

Rajendhran³

et al. 2018

J Material Sci Eng

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The curcumin loaded PMMA-AA/ZnO nanocomposite potentially inhibited the growth of AGS cancer tumour in male Swiss albino mouse, which showed a promising targeted cancer therapy. Interestingly the given bio-nanocomposite was rapidly cleared from the organs with negligible exhibition of toxicity. From the obtained results it is understood that the apoptosis has been occurred through mitochondrial disruption-mediated pathway. Also these nanomaterials could efficiently hinder the Go/G1 transition along with cycle progression at S-phase transition due to the radiation-induced DNA damage. These findings declared that the auspicious candidate, curcumin could be successfully delivered into the target by the polymer encapsulated ZnO NPs and exhibited a potent activity against gastric cancer cells at molecular and cellular levels as well as cell proliferation in a panel of tumour cells.

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Effect of molecular weight of PGG–paclitaxel conjugates on in vitro and in vivo efficacy

Cited by 43 publications

References 31 publications

Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel–Conjugate Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D Models

Core-Cross-Linking Accelerates Antitumor Activities of Paclitaxel–Conjugate Micelles to Prostate Multicellular Tumor Spheroids: A Comparison of 2D and 3D Models

Polymeric complex micelles with double drug-loading strategies for folate-mediated paclitaxel delivery

pH Triggered Curcumin Release from PMMA-AA Coated ZnO Nanoparticles for Excellent Anti-Gastric Cancer Therapy

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