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A chitosan-modified graphene nanogel for noninvasive controlled drug release.

ABSTRACT: A near infrared (NIR) triggered drug delivery platform based on the chitosan-modified chemically reduced graphene oxide (CRGO) incorporated into a thermosensitive nanogel (CGN) was developed. CGN exhibited an NIR-induced thermal effect similar to that of CRGO, reversible thermo-responsive characteristics at 37-42 °C and high doxorubicin hydrochloride (DOX) loading capacity (48 wt%). The DOX loaded CGN (DOX-CGN) released DOX faster at 42 °C than at 37 °C. The fluorescence images revealed DOX expression in the cytoplasm of cancer cells when incubated with DOX-CGN at 37 °C but in the nucleus at 42 °C. Upon irradiation with NIR light (808 nm), a rapid, repetitive DOX release from the DOX-CGN was observed. Furthermore, the cancer cells incubated with DOX-CGN and irradiated with NIR light displayed significantly greater cytotoxicity than without irradiation owing to NIR-triggered increase in temperature leading to nuclear DOX release. These results demonstrate CGN's promising application for on-demand drug release by NIR light.These investigators report the successful development of a novel near infrared triggered drug delivery platform based on chitosan-modified chemically reduced graphene oxide (CRGO) incorporated into a thermosensitive nanogel (CGN).

SUBMITTER: Wang C

PROVIDER: S-EPMC3783966 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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A chitosan-modified graphene nanogel for noninvasive controlled drug release.

Wang Chunyan C Mallela Jaya J Garapati Ujjwala Sree US Ravi Sowndharya S Chinnasamy Vignesh V Girard Yvonne Y Howell Mark M Mohapatra Subhra S

Nanomedicine : nanotechnology, biology, and medicine 20130122 7

A near infrared (NIR) triggered drug delivery platform based on the chitosan-modified chemically reduced graphene oxide (CRGO) incorporated into a thermosensitive nanogel (CGN) was developed. CGN exhibited an NIR-induced thermal effect similar to that of CRGO, reversible thermo-responsive characteristics at 37-42 °C and high doxorubicin hydrochloride (DOX) loading capacity (48 wt%). The DOX loaded CGN (DOX-CGN) released DOX faster at 42 °C than at 37 °C. The fluorescence images revealed DOX expr ...[more]

PMID: 23352802

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Project description:Chitosan nanofibrous membranes have immense potential in tissue engineering and drug delivery applications because of their increased surface area, high degree of biocompatibility, and their ability to mimic the extracellular matrix. However, their use is often limited due to their extreme hydrophilic nature causing them to lose their nanofibrous structure in vivo. In the present study, chitosan membranes were modified either by acylation reactions using fatty acids of different chain lengths or tert-butyloxycarbonyl (tBOC) protecting groups to increase the hydrophobicity of the membranes and protect the nanofibrous structure. The modified membranes were characterized using scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, water contact angle and elemental analysis to confirm the addition of the modification groups. These membranes were then evaluated to control the release of a hydrophobic osteogenic drug-simvastatin (SMV). The interaction between SMV and the polymer was determined using molecular modeling. Pure SMV and SMV loaded membranes were examined for their in vitro cytotoxicity and osteogenic potential using preosteoblast mouse bone marrow stromal cells. From results, it was evident that as the fatty acid chain length increased from two to six methylene groups, the hydrophobicity of the membranes increased (59.2 ± 8.2° to 94.3 ± 8.5° water contact angle). The amount of drug released from the membranes could be controlled by changing the amount of initial drug loaded and/or the type of modifications. After 4 weeks, for a 500 μg loading, the short chain fatty acid modified membranes released 17.8 ± 3.2% of the drug whereas a long chain fatty acid released only 4.8 ± 0.8%. Similarly, for a 50 μg loading, short chain modified membranes released more (73.3 ± 33.3%) of the loaded drug as compared to the long chain membranes (43.0 ± 3.5%). The long chain fatty acid membranes released SMV for extended time periods of up to 90 days. This data was further supported by molecular modeling, which revealed that SMV was more compatible with more hydrophobic membranes. Cell studies showed that pure SMV from 75 to 600 ng/ml range possessed osteogenic potential in a dose dependent manner and the amount of SMV released from the most hydrophobic FA treated membranes was not cytotoxic and supported osteogenic differentiation. Therefore, this study demonstrates our ability to control the release of a hydrophobic drug from modified chitosan membranes as per the clinical need.

Project description:Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

Dataset Information

A chitosan-modified graphene nanogel for noninvasive controlled drug release.

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A chitosan-modified graphene nanogel for noninvasive controlled drug release.

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