Discriminated effects of thiolated chitosan-coated pMMA paclitaxel-loaded nanoparticles on different normal and cancer cell lines

Akhlaghi, Seyedeh Parinaz; Saremi, Shahrooz; Ostad, Seyed Nasser; Dinarvand, Rassoul; Atyabi, Fatemeh

doi:10.1016/j.nano.2010.01.011

Cited by 73 publications

(38 citation statements)

References 28 publications

(27 reference statements)

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“…In our previous study, it was shown that the blank NPs did not show any cytotoxic effect on the Caco-2 and MCF-7 cells. 44 The results in this study indicated that the drug entrapped in thiolated Chito.20 NPs had more cytotoxic effect than the free drug for Caco-2 cells at most concentrations (P , 0.05) and had equal cytotoxicity for MCF-7 after 72 hours. Based on the result of in vitro release studies (Figure 4), after 72 hours, approximately 70% of the drug is released from the NPs.…”

Section: In Vitro Drug Release Studymentioning

confidence: 57%

Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel: preparation, in vitro and ex vivo evaluation

Saremi

Atyabi

Akhlaghi³

et al. 2011

IJN

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The aim of this study was to prepare and evaluate mucoadhesive core-shell nanoparticles based on copolymerization of thiolated chitosan coated on poly methyl methacrylate cores as a carrier for oral delivery of docetaxel. Docetaxel-loaded nanoparticles with various concentrations were prepared via a radical emulsion polymerization method using cerium ammonium nitrate as an initiator. The physicochemical properties of the obtained nanoparticles were characterized by: dynamic light-scattering analysis for their mean size, size distribution, and zeta potential; scanning electron microscopy and transmission electron microscopy for surface morphology; and differential scanning calorimetry analysis for confirmation of molecular dispersity of docetaxel in the nanoparticles. Nanoparticles were spherical with mean diameter below 200 nm, polydispersity of below 0.15, and positive zeta potential values. The entrapment efficiency of the nanoparticles was approximately 90%. In vitro release studies showed a sustained release characteristic for 10 days after a burst release at the beginning. Ex vivo studies showed a significant increase in the transportation of docetaxel from intestinal membrane of rat when formulated as nanoparticles. Cellular uptake of nanoparticles was investigated using fluoresceinamine-loaded nanoparticles. Docetaxel nanoparticles showed a high cytotoxicity effect in the Caco-2 and MCF-7 cell lines after 72 hours. It can be concluded that by combining the advantages of both thiolated polymers and colloidal particles, these nanoparticles can be proposed as a drug carrier system for mucosal delivery of hydrophobic drugs.

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Section: In Vitro Drug Release Studymentioning

confidence: 57%

Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel: preparation, in vitro and ex vivo evaluation

Saremi

Atyabi

Akhlaghi³

et al. 2011

IJN

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“…The amount of paclitaxel loaded onto MWNT-g-PCA-PTX was quantified by an indirect method 28 whereby free paclitaxel after the reaction with MWNT-g-PCA that accumulated in the dialysis medium was analyzed. In this way, the amount of conjugated paclitaxel to the MWNT-g-PCA was estimated according to the initial amount of drug.…”

Section: Paclitaxel Content Of the Conjugatementioning

confidence: 99%

Increased paclitaxel cytotoxicity against cancer cell lines using a novel functionalized carbon nanotube

Sobhani¹,

Dinarvand²,

Atyabi³

et al. 2011

IJN

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Potential applications of carbon nanotubes have attracted many researchers in the field of drug delivery systems. In this study, multiwalled carbon nanotubes (MWNTs) were first functionalized using hyperbranched poly citric acid (PCA) to improve their hydrophilicity and functionality. Then, paclitaxel (PTX), a potent anticancer agent, was conjugated to the carboxyl functional groups of poly citric acid via a cleavable ester bond to obtain a MWNT- g -PCA-PTX conjugate. Drug content of the conjugate was about 38% (w/w). The particle size of MWNT- g -PCA and MWNT- g -PCA-PTX was approximately 125 and 200 nm, respectively. Atomic force microscopy and transmission electron microscopy images showed a curved shape for MWNT- g -PCA and MWNT- g -PCA-PTX, which was in contrast with the straight or linear conformation expected from carbon nanotubes. It seems that the high hydrophilicity of poly citric acid and high hydrophobicity of MWNTs led to conformational changes from a linear state to a curved state. Paclitaxel can be released from the MWNT- g -PCA-PTX conjugates faster at pH 6.8 and 5.0 than at pH 7.4, which was suitable for the release of the drug in tumor tissues and tumor cells. In vitro cytotoxicity studies were evaluated in the A549 and SKOV3 cell lines. MWNT- g -PCA had an insignificant cytotoxic effect on both cell lines. MWNT- g -PCA-PTX had more of a cytotoxic effect than the free drug over a shorter incubation time (eg, 24 hours versus 48 hours), which suggests improved cell penetration of MWNT- g -PCA-PTX. Therefore, paclitaxel conjugated to MWNT- g -PCA is promising for cancer therapeutics.

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“…[18][19][20] Chitosan is a carbohydrate polymer with the desirable properties of biodegradability and biocompatibility that have made it a candidate polymer for preparation of drug delivery carriers. [21][22][23][24][25][26][27][28][29] Several methods have been developed for the preparation of doxorubicin delivery systems based on chitosan, 30 which include dextran sulfate-chitosan hydrogel nanoparticles, glycol-chitosan nanoaggregates, oleoyl-chitosan nanoparticles, chitosan-poly(acrylic acid) hollow nanospheres, and stearic acid-grafted chitosan oligosaccharide micelles.…”

Section: Introductionmentioning

confidence: 99%

Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

Sakhtianchi¹,

Atyabi²,

Yousef³

et al. 2011

IJN

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Background Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action. Methods Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX) nanoparticles (particle size, 200 nm) via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles. Results CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb) contained 47 μg/mg doxorubicin and 33.5 μg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and selective uptake of CS-DOX-mAb by Her2 + cancer cells compared with nontargeted CS-DOX nanoparticles and free drug. Conclusion Antibody-conjugated nanoparticles were shown to discriminate between Her2 + and Her2 − cells, and thus have the potential to be used in active targeted drug delivery, with reduction of drug side effects in Her2 + breast and ovarian cancers.

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Discriminated effects of thiolated chitosan-coated pMMA paclitaxel-loaded nanoparticles on different normal and cancer cell lines

Cited by 73 publications

References 28 publications

Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel: preparation, in vitro and ex vivo evaluation

Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel: preparation, in vitro and ex vivo evaluation

Increased paclitaxel cytotoxicity against cancer cell lines using a novel functionalized carbon nanotube

Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

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