A novel dual-responsive core-crosslinked magnetic-gold nanogel for triggered drug release.

A facial approach was reported to prepare a novel dual-responsive core-crosslinked nanogel and investigated for the triggered methotrexate (MTX) release. Nanogels with core-shell architecture were synthesized by decoration of Au/Fe3O4 core/shell NPs using poly(ethylene glycol)-b-poly((N,N-dimethylamino)ethyl methacrylate-co-2-hydroxyethyl methacrylate)-maleic acid (PEG-b-P(DMAEMA-co-HEMA)-MA) for crosslinking and autoreduction processes. The second block containing amino groups and maleate groups as the inner shell was used for the reduction of HAuCl4 (auric cation) in the presence of Fe3O4 NPs and as a crosslinker agent, respectively. Furthermore, to improve the long-term dispersibility of the nanogels, poly(ethylene glycol) was preferred as outer shell even under high ionic strength. After that, NIPAAm was polymerized from the vinyl double bonds for fabricating the thermo and pH-responsive core-crosslinked nanogels. MTX (an anti-cancer agent) was successfully loaded (the loading capacity of 37%) into the nanogels by both ionic interaction and entrapment in polymeric network in the inner shell. The triggered MTX release ability of the synthesized nanocarriers was proved through the comparison of in-vitro drug release at simulated physiological condition and tumor tissue environment. MTT assay showed that MTX-loaded nanocarriers revealed high antitumor activity in MCF7 cell line after incubation following 24 and 48h. It was concluded that the developed nanogels have many promising qualities as an efficient carrier for the targeted MTX delivery to cancer tissues.

Fabrication of biodendrimeric ß-cyclodextrin via click reaction with potency of anticancer drug delivery agent.

The aim of this work was the synthesis of biodendrimeric ß-cyclodextrin (ß-CD) on the secondary face with encapsulation efficacy, with ß-CDs moiety to preserve the biocompatibility properties, also particularly growth their loading capacity for drugs with certain size. The new dendrimer, having 14 ß-CD residues attached to the core ß-CD in secondary face (11), was prepared through click reaction. The encapsulation property of the prepared compound was evaluated by methotrexate (MTX) drug molecule. Characterization of compound 11 was performed with (1)H NMR, (13)C NMR and FTIR and its supramolecular inclusion complex structure was determined using FTIR, DLS, DSC and SEM techniques. In vitro cytotoxicity test results showed that compound 11 has very low or no cytotoxic effect on T47D cancer cells. In vitro drug release study at pHs 3, 5 and 7.4 showed that the release process was noticeably pH dependent and the dendrimer could be used as an appropriate controlled drug delivery system (DDS) for cancer treatment.

Development of a novel controlled-release nanocomposite based on poly(lactic acid) to increase the oxidative stability of soybean oil.

A poly(lactic acid) (PLA)-based nanocomposite active packaging was developed for the controlled release of tert-butylhydroquinone (TBHQ) antioxidant. The PLA-based active films were loaded with only TBHQ (3% wt) or a mixture of modified cellulose nanofibre (MCNF) (8% wt) and TBHQ (3% wt) to obtain active and nanocomposite active films, respectively. Release studies indicated that the release rate of TBHQ in 95% ethanol simulant was significantly decreased by the addition of MCNF. Moreover, the presence of MCNF diminished the increasing effect of temperature on the release rate as when storage temperature increased from 4°C to 40°C. The diffusion coefficient (D) for PLA-TBHQ and PLA-MCNF-TBHQ films increased from 6.75 and 4.34 × 10(-8) cm(2) s(-1) to 19.85 and 8.49 × 10(-8) cm(2) s(-1), respectively. Diffusion of TBHQ to soybean oil was enough to delay the induction of the oxidation of soybean oil stored for 6 months in contact with PLA-based films. Antioxidative activity of PLA-based active films considerably increased with increasing storage time as indicated by the increase in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and the oxidative stability index (p < 0.05). This study demonstrates that effective controlled release antioxidant packaging could be obtained by using MCNF nanofiller, which leads to prolonged activity and an extended shelf-life in fatty foods.

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.