Core-Sheath Nanofibers as Drug Delivery System for Thermoresponsive Controlled Release.

In this work, a smart drug delivery system of core-sheath nanofiber is reported. The core-sheath nanofibers were prepared with thermoresponsive poly-(N-isopropylacrylamide) (as core) and hydrophobic ethyl cellulose (as sheath) by coaxial electrospinning. Analogous medicated fibers were prepared by loading with a model drug ketoprofen (KET). The fibers were cylindrical without phase separation and have visible core-sheath structure as shown by scanning and transmission electron microscopy. X-ray diffraction patterns demonstrated the drug with the amorphous physical form was present in the fiber matrix. Fourier transform infrared spectroscopy analysis was conducted, finding that there were significant intermolecular interactions between KET and the polymers. Water contact angle measurements proved that the core-sheath fibers from hydrophilic transformed into hydrophobic when the temperature reached the lower critical solution temperature. In vitro drug-release study of nanofibers with KET displayed that the coaxial nanofibers were able to synergistically combine the characteristics of the 2 polymers producing a temperature-sensitive drug delivery system with sustained-release properties. In addition, they were established to be nontoxic and suitable for cell growth. These findings show that the core-sheath nanofiber is a potential candidate for controlling drug delivery system.

Targeted delivery and controlled release of doxorubicin into cancer cells using a multifunctional graphene oxide.

We have synthesized a new multifunctional graphene oxide as a drug carrier targeting to hepatocarcinoma cells. Surface modified graphene oxide with polyethyleneimine (PEI) sequentially derivatised with fluorescein isothiocyanate (FI) and polyethylene glycol (PEG)-linked lactobionic acid (LA), and acetylation of remaining terminal amines of the PEI produced a new multifunctional graphene oxide drug carrier (GO/PEI.Ac-FI-PEG-LA). Doxorubicin (DOX), an anticancer drug, was encapsulated in GO/PEI.Ac-FI-PEG-LA to give GO/PEI.Ac-FI-PEG-LA/DOX, with a drug loading percentage of 85%. We showed that both GO/PEI.Ac-FI-PEG-LA and GO/PEI.Ac-FI-PEG-LA/DOX were water soluble and stable between pH 5.0 and 9.0. In vitro release studies indicated that the release rate of DOX from GO/PEI.Ac-FI-PEG-LA/DOX complexes were significantly higher at pH5.8 than that of the physiological pH. Another important feature of this carrier is its good cell viability in the tested concentration range (0-4µM), and the GO/PEI.Ac-FI-PEG-LA/DOX can specifically target cancer cells overexpressing asialoglycoprotein (ASGPR) receptors and exert growth inhibition effect to the cancer cells. The enhanced target specificity and the substantial improvement in pH responsive controlled release have made this new carrier a potential choice for non-covalent encapsulation of drugs in GO, and a delivery system for cancer therapy.

Lactobionic acid and carboxymethyl chitosan functionalized graphene oxide nanocomposites as targeted anticancer drug delivery systems.

In this work, we report a targeted drug delivery system built by functionalizing graphene oxide (GO) with carboxymethyl chitosan (CMC), fluorescein isothiocyanate and lactobionic acid (LA). Analogous systems without LA were prepared as controls. Doxorubicin (DOX) was loaded onto the composites through adsorption. The release behavior from both the LA-functionalized and the LA-free material is markedly pH sensitive. The modified GOs have high biocompatibility with the liver cancer cell line SMMC-7721, but can induce cell death after 24h incubation if loaded with DOX. Tests with shorter (2h) incubation times were undertaken to investigate the selectivity of the GO composites: under these conditions, neither DOX-loaded system was found to be toxic to the non-cancerous L929 cell line, but the LA-containing composite showed the ability to selectively induce cell death in cancerous (SMMC-7721) cells while the LA-free analogue was inactive here also. These findings show that the modified GO materials are strong potential candidates for targeted anticancer drug delivery systems.