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      Injectable doxorubicin-loaded hydrogels based on dendron-like β-cyclodextrin–poly(ethylene glycol) conjugates

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          Abstract

          Dendron-like CD–PEG conjugates with multiple acrylates were synthesized facilely, which can incorporate adamantane-modified doxorubicin and further be crosslinked by POEGMS, to give injectable doxorubicin-loaded hydrogels.

          Dendron-like multifunctional β-cyclodextrin–poly(ethylene glycol) (CD–PEG) conjugates were synthesized from amino functionalized β-cyclodextrins and poly(ethylene glycol) diacrylate through the Michael addition reaction. The resultant conjugates contain several PEG arms terminated with acrylates, which originated from the same glucopyranose unit of CD. These dendron-like CD–PEG conjugates can incorporate adamantane-modified doxorubicin (AD–DOX) by host–guest interactions between CD and AD moieties, to give a reactive supramolecular polymeric prodrug, which can be further crosslinked by poly[oligo(ethylene glycol) mercaptosuccinate] (POEGMS) via thiol–ene “click” reaction under physiological conditions. These kinds of in situ forming drug-loaded hydrogels can be utilized as injectable gelling carriers for localized drug delivery.

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          Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.

          Leonard Saltz, Stephen Clarke, Eduardo Díaz-Rubio … (2008)
          To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC). Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS). A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials. The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.
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            Injectable hydrogels as unique biomedical materials.

            Lin Yu, Jiandong Ding (2008)
            A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.
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              Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective.

              Jianxiang Zhang, Peter Ma (2013)
              The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed.
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                Author and article information

                Journal
                Journal ID (publisher-id): PCOHC2
                Title: Polymer Chemistry
                Abbreviated Title: Polym. Chem.
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 1759-9954
                ISSN (Electronic): 1759-9962
                Publication date Created: 2017
                Publication date (Print): 2017
                Volume: 8
                Issue: 10
                Pages: 1680-1688
                Article
                DOI: 10.1039/C6PY02243J
                SO-VID: e3079fff-020b-4b5e-82ab-e9be210c9983
                Copyright © © 2017
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