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Polymer-drug conjugates have played an important role in improving tumor cell targeting and the selectivity of anticancer drugs. In this study, quantum dots and melphalan were attached to the backbone of hyaluronic acid to synthesize a polymer-drug conjugate. The physicochemical properties of the conjugate were characterized by FT-IR, XRD, (1)H NMR, UV-Vis spectra and DLS. The in vitro drug release profiles and cell evaluation were investigated. The results showed that the conjugate was synthesized and self-assembled into nanoparticles with a diameter of 115 ± 2.3 nm. The conjugate had a pH-sensitive drug controlled release property. It was an ideal receptor-mediated delivery system and can be internalized into the human breast cancer cell. It had a better inhibition effect on human breast cancer cell and a poorer inhibition effect on normal breast cell than melphalan. These results supported that the conjugate would be a promising candidate for cancer therapy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The clinical application of melphalan (Me), an anticancer drug for the treatment of hematologic malignancies, has been limited due to its poor water solubility, rapid elimination and lack of target specificity. To solve these problems, O,N-carboxymethyl chitosan-peptide-melphalan conjugates were synthesized and characterized. All polymeric prodrugs showed satisfactory water solubility. It was found that the molecular weight of O,N-carboxymethyl chitosan (O,N-CMCS) and the peptide spacer played a crucial role in controlling the drug content, diameter and drug release properties of O,N-carboxymethyl chitosan-peptide-melphalan conjugates. The studies of in vitro drug release and cell cytotoxicity by MTT assay revealed that, employing the polymeric conjugation strategy and using the peptides glycylglycine (Gly-Gly) as a spacer, the conjugates have good cathepsin X-sensitivity and lower toxicity and the drug release behavior improved remarkably. In conclusion, O,N-carboxymethyl chitosan-peptide-melphalan conjugates could be promising prodrugs for anticancer application., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A series of melphalan-O-carboxymethyl chitosan (Mel-OCM-chitosan) conjugates with different spacers were prepared and structurally characterized. All conjugates showed satisfactory water-solubility (160-217 times of Mel solubility). In vitro drug release behaviors by both chemical and enzymatic hydrolysis were investigated. The prodrugs released Mel rapidly within papain and lysosomal enzymes of about 40-75%, while released only about 4-5% in buffer and plasma, which suggested that the conjugates have good plasma stability and the hydrolysis in both papain and lysosomes occurs mostly via enzymolysis. It was found that the spacers have important effect on the drug content, water solubility, drug release properties and cytotoxicity of Mel-OCM-chitosan conjugates. Cytotoxicity studies by MTT assay demonstrated that these conjugates had 52-70% of cytotoxicity against RPMI8226 cells in vitro as compared with free Mel, indicating the conjugates did not lose anti-cancer activity of Mel. Overall these studies indicated Mel-OCM-chitosan conjugates as potential prodrugs for cancer treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Prodrug development is an important strategy for improving tumor cell targeting and the selectivity of anticancer drugs. In this study, poly(ethylene glycol) and melphalan, an anticancer drug, were linked to the backbone of hyaluronic acid via amide bonds using carbodiimide chemistry to synthesize a poly(ethylene glycol)–hyaluronic acid–melphalan prodrug. The physicochemical properties of the prodrug were characterized by Fourier transform infrared, proton nuclear magnetic resonance, ultraviolet–visible spectroscopy, and dynamic light scattering and transmission electron microscopy. The in vitro drug release profiles and the corresponding in vitro cell evaluation of the prodrug were investigated. The poly(ethylene glycol)–hyaluronic acid–melphalan prodrug was successfully synthesized and self-assembled into 116.4-nm nanoparticles. The release profiles demonstrated that controlled release of the prodrug could be achieved with a sensitive property involving both pH and enzymatic degradation. The poly(ethylene glycol)–hyaluronic acid–melphalan prodrug was more effectively transferred into the ovarian tumor cell (SKOV3) than into human ovarian fibroblast (HOF) cells. It also had a higher inhibition effect on SKOV3 and a lower inhibition effect on HOF than melphalan. This poly(ethylene glycol)–hyaluronic acid–melphalan prodrug, with its controlled release properties and selectivity, is a promising drug delivery system for cancer therapy. [ABSTRACT FROM PUBLISHER]