pH-sensitive curcumin conjugated micelles for tumor triggered drug delivery.

Development of new drugs are confronted with some barriers and challenges, since these projects are mainly expensive, complex, time consuming with lack of success, there is an urgent need to reformulate the current poorly water soluble anti-cancer drugs. In this study, a new type of polymer-curcumin conjugates based on glycidyl azide polymer (GAP) was developed for cancer therapy. The copolymer was used for delivery of curcumin (CUR) as an anticancer drug to cancer cells. Our method is based on the facile conjugation of CUR to amine-containing polymeric vehicles through imine linkage bonds, which could remain stable in normal physiological condition while readily dissociate by an acidic environment and make the prodrug active to liberate its payload CUR to inhibit cell growth. The results demonstrated that fabricated amphiphilic PDCs were self-assembled into nanosized micelles in aqueous solution and the micelles showed an average size of 180 nm with a good polydispersity index. Drug release studies demonstrated that this nano-conjugate is fairly stable at physiologic environments but prone to mild acidic conditions which would trigger the release of conjugated CUR. Moreover, the PDCs micelles exhibited excellent cytotoxicity effect on 4T1 mouse breast cancer cell line but no significant toxicity was observed for the copolymer. In addition, the copolymer did not display remarkable toxicity against A. salina even at high doses of copolymer. In addition, the synthesized PDCs exhibited hemolysis lowers than 6%. The safety of copolymers as a drug vehicle was also confirmed by LD50, since all mice which treated with 5000 mg/Kg (limited dose) were still alive after one week. Our findings revealed that these unique pH-sensitive PDCs may provide a promising approach for delivery of the anticancer drugs to cancer cells.[Formula: see text].

pH-Sensitive Magnetite Nanoparticles Modified with Hyperbranched Polymers and Folic Acid for Targeted Imaging and Therapy.

OBJECTIVE: A novel pH-sensitive superparamagnetic drug delivery system was developed based on quercetin loaded hyperbranched polyamidoamine-b-polyethylene glycol-folic acid-modified Fe3O4 nanoparticles (Fe3O4@PAMAM-b-PEG-FA). METHODS: The nanoparticles exhibit excellent water dispersity with well-defined size distribution (around 51.8 nm) and strong magnetisability. In vitro release studies demonstrated that the quercetinloaded Fe3O4@PAMAM-b-PEG-FA nanoparticles are stable at normal physiologic conditions (pH 7.4 and 37°C) but sensitive to acidic conditions (pH 5.6 and 37°C), which led to the rapid release of the loaded drug. RESULTS: Fluorescent microscopy results indicated that the Fe3O4@PAMAM-b-PEG-FA nanoparticles could be efficiently accumulated in tumor tissue compared with non-folate conjugated nanoparticles. Also, in comparison with free quercetin, the quercetin loaded Fe3O4@PAMAM-b-PEG-FA exerts higher cytotoxicity. Furthermore, this magnetic nanocarrier showed high MRI sensitivity, even in its lower iron content. CONCLUSION: The results indicated that the prepared nanoparticles are an effective chemotherapy and diagnosis system to inhibit proliferation and monitor the progression of tumor cells, respectively.

Folate-decorated thermoresponsive micelles based on star-shaped amphiphilic block copolymers for efficient intracellular release of anticancer drugs.

In this study, a new type of folate-decorated thermoresponsive micelles based on the star-shaped amphiphilic block copolymer 4s[poly(ε-caprolactone)-b-2s(poly(N-isopropylacrylamide-co-acrylamide)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate)] (i.e., 4s[PCL-b-2s(P(NIPAAm-co-AAm)-b'-MPEG/PEG-FA)] (PCIAE-FA)), were developed for the tumor-targeted delivery and temperature-induced controlled release of hydrophobic anticancer drugs. These amphiphilic star copolymers are capable of self-assembling into spherical micelles in aqueous solution with an average diameter of 91 nm. The lower critical solution temperature (LCST) of micelles was around 39.7 °C. The anticancer drug, paclitaxel (PTX), was encapsulated into the micelles. In vitro release studies demonstrated that the drug-loaded delivery system (PTX-PCIAE-FA) is relatively stable at physiologic conditions but susceptible to temperatures above LCST which would trigger the release of encapsulated drugs. The cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol(®). The efficacy of this thermoresponsive drug delivery system was also evaluated at temperatures above the LCST; the results demonstrated that the cellular uptake and the cytotoxicity of PTX-loaded micelles increase prominently. These results indicate that these thermoresponsive micelles may offer a very promising carrier to improve the delivery efficiency and cancer specificity of hydrophobic chemotherapeutic drugs.