Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

Prabaharan, M.; Grailer, Jamison; Pilla, Srikanth; Steeber, Douglas A.; Gong, Shaoqin

doi:10.1016/j.biomaterials.2009.02.011

Cited by 319 publications

(218 citation statements)

References 40 publications

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“…Given these beneficial properties, HBPDCs are excellent candidates for high drug-loading nanomedicine fabrication. [151][152][153] Prabaharan et al 154 synthesized the first HBPDC nanomedicines in 2009. In their work, a folate-targeting unimolecular micelle nanomedicine was synthesized, namely Boltorn H40-poly(l-aspartate-doxorubicin)-b-PEG/FA-conjugated PEG (H40-P[LA-Dox]-b-PEG-OH/FA).…”

Section: Branched Polymer-drug Conjugatesmentioning

confidence: 99%

High drug-loading nanomedicines: progress, current status, and prospects

Shen

Liu

et al. 2017

IJN

423

268

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Drug molecules transformed into nanoparticles or endowed with nanostructures with or without the aid of carrier materials are referred to as “nanomedicines” and can overcome some inherent drawbacks of free drugs, such as poor water solubility, high drug dosage, and short drug half-life in vivo. However, most of the existing nanomedicines possess the drawback of low drug-loading (generally less than 10%) associated with more carrier materials. For intravenous administration, the extensive use of carrier materials might cause systemic toxicity and impose an extra burden of degradation, metabolism, and excretion of the materials for patients. Therefore, on the premise of guaranteeing therapeutic effect and function, reducing or avoiding the use of carrier materials is a promising alternative approach to solve these problems. Recently, high drug-loading nanomedicines, which have a drug-loading content higher than 10%, are attracting increasing interest. According to the fabrication strategies of nanomedicines, high drug-loading nanomedicines are divided into four main classes: nanomedicines with inert porous material as carrier, nanomedicines with drug as part of carrier, carrier-free nanomedicines, and nanomedicines following niche and complex strategies. To date, most of the existing high drug-loading nanomedicines belong to the first class, and few research studies have focused on other classes. In this review, we investigate the research status of high drug-loading nanomedicines and discuss the features of their fabrication strategies and optimum proposal in detail. We also point out deficiencies and developing direction of high drug-loading nanomedicines. We envision that high drug-loading nanomedicines will occupy an important position in the field of drug-delivery systems, and hope that novel perspectives will be proposed for the development of high drug-loading nanomedicines.

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Section: Branched Polymer-drug Conjugatesmentioning

confidence: 99%

High drug-loading nanomedicines: progress, current status, and prospects

Shen

Liu

et al. 2017

IJN

423

268

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“…Implementing synthesis schemes that aid in maintaining maximum epirubicin-(C 3 -amide)-[anti-HER2/neu] bindingavidity for surface membrane HER2/neu serves to optimize the magnitude of selective ''targeted'' epirubicin delivery at HER2/neu trophic receptors highly overexpressed by mammary adenocarcinoma SKBr-3 populations. Second, maintaining maximum binding-avidity also directly facilitates efficient and more extensive internalization of epirubicin-(C 3 -amide)-[anti-HER2/neu] by mechanisms of ligand-induced receptor-mediated-endocytosis at HER2/neu overexpressed by mammary adenocarcinoma 7,26,30,120 and other neoplastic cell types. [121][122][123][124][125] Seemingly modest alterations in synthetic chemistry conditions, and elevations in chemotherapeutic molar-incorporation-indexes can profoundly influence the selective binding properties of immunoglobulin fractions.…”

Section: Cell-elisa Membrane Igg Binding Analysismentioning

confidence: 99%

Synthesis of a Covalent Epirubicin-(C₃-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Coyne

Jones²,

Bear³

2012

Cancer Biotherapy and Radiopharmaceuticals

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The C 3 -monoamine on the carbohydrate moiety (daunosamine -NH 2 -3¢) of epirubicin was reacted under anhydrous conditions with succinimidyl 4,4-azipentanoate to create a covalent UV-photoactivated epirubicin-(C 3 -amide) intermediate with primary amine-reactive properties. A synthetic covalent bond between the UV-photoactivated epirubicin-(C 3 -amide) intermediate and the e-amine of lysine residues within the amino acid sequence of anti-HER2/neu monoclonal immunoglobulin was subsequently created by exposure to UV light (354 nm) for 15 minutes. Size-separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunodetection analysis and chemiluminescent autoradiographic imaging revealed a lack of IgG-IgG polymerization or degradative protein fragmentation of the covalent epirubicin-(C 3 -amide)-[anti-HER2/neu] immunochemotherapeutic. Retained binding-avidity of epirubicin-(C 3 -amide)-[anti-HER2/neu] was validated by cell-ELISA utilizing monolayer populations of chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 which highly overexpress membrane-associated HER2/neu complexes. Between epirubicin-equivalent concentrations of 10 -10 to 10 -6 M the covalent epirubicin-(C 3 -amide)-[anti-HER2/neu] immunochemotherapeutic consistently evoked levels of cytotoxic anti-neoplastic potency that were highly analogous to chemotherapeuticequivalent concentrations of epirubicin. Cytotoxic anti-neoplastic potency of epirubicin-(C 3 -amide)-[anti-HER2/ neu] against chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 challenged with epirubicin-(C 3 -amide)-[anti-HER2/neu] at an epirubicin-equivalent concentration of 10 -6 M was 88.5% (e.g., 11.5% residual survival). Between final epirubicin-equivalent concentrations of 10 -8 and 10 -7 M there was a marked threshold increase in the mean cytotoxic anti-neoplastic activity for epirubicin-(C 3 -amide)-[anti-HER2/neu] from 9.9% to 66.9% (90.2% to 33.1% residual survival).

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“…It is noted that copolymers such as dendrimers (Medina & El-Sayed, 2009;Pan et al, 2009;Abderrezak et al, 2012), linear-b-dendritic block copolymers (Wurm & Frey, 2011), star block copolymers (Prabaharan et al, 2009a) and brush copolymers (Prabaharan et al, 2009b;Yan et al, 2009) have been studied as vehicles for drug loading and delivery. In comparison with linear polymers, these branched polymers have a greater effect on the physico-chemical characteristics of the polymer itself as well as drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

et al. 2014

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(2015) Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin, Drug Delivery, 22:1, 58-68, DOI: 10.3109/10717544.2014 Methods: A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly ("-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and "-caprolactone as raw materials. Its structure was characterized by 1 H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out. Results: Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 Â 10 5 times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model (R 2 abj ¼ 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT 0-1 , t 1/2z and AUC 0-1 of Curcuminloaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution. Conclusions: The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR.

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Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

Cited by 319 publications

References 40 publications

High drug-loading nanomedicines: progress, current status, and prospects

High drug-loading nanomedicines: progress, current status, and prospects

Synthesis of a Covalent Epirubicin-(C₃-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

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Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

Cited by 319 publications

References 40 publications

High drug-loading nanomedicines: progress, current status, and prospects

High drug-loading nanomedicines: progress, current status, and prospects

Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Contact Info

Product

Resources

About

Synthesis of a Covalent Epirubicin-(C₃-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate