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Gemcitabine hydrochloride-loaded functionalised carbon nanotubes as potential carriers for tumour targeting.

Das S, Desai JL, Thakkar HP - Indian J Pharm Sci (2013)

Bottom Line: Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern.Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride.Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.

View Article: PubMed Central - PubMed

Affiliation: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara-390 001, India.

ABSTRACT
The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of -10-1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.

No MeSH data available.


Related in: MedlinePlus

FT-IR spectrum of MWCNTs.FT-IR spectrum of MWCNTs (a), DSPE-mPEG2000 (b) and f-CNTs (c).
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Figure 2: FT-IR spectrum of MWCNTs.FT-IR spectrum of MWCNTs (a), DSPE-mPEG2000 (b) and f-CNTs (c).

Mentions: The sidewalls of CNTs are highly hydrophobic because of which it is difficult to disperse them both in aqueous and organic media. For the use of CNTs as carriers for drug delivery, it is often necessary to disperse them uniformly in aqueous medium. Hence, functionalisation of CNTs was carried out to impart dispersibility to CNTs in different media. Moreover, for functionalisation PEG was used, which also provides reduced reticuloendothelial system (RES) uptake resulting in prolonged circulation in blood. This property was attributed to the irreversible surface adsorption of PEG molecules on MWCNTs[29]. This surface adsorption was possible by using DSPE, which attaches noncovalently to both CNTs surface and PEG molecules. Hence, DSPE-mPEG2000 was used for functionalisation of MWCNTs in ratio of 1:2 w/w of DSPE:mPEG2000. Different batches prepared with varying ratios of CNTs:DSPE-mPEG2000 revealed that initially particle size of formulation decreased as the amount of DSPE-mPEG2000 increased up to the ratio of 1:2 of CNTs:DSPE-mPEG2000. Further when the amount of DSPE-mPEG2000 was increased, the particle size also increased and reaggregation was observed after 1:4.5 ratio due to presence of excess of DSPE-mPEG2000. Desirable particle size of 178.23 nm (Table 1) was found in ratio of 1:2, hence this CNTs: DSPE-mPEG2000 was taken as optimised ratio and was used for loading of GEM HCl and further characterisation. The f-CNTs had better dispersibility than CNTs because of PEGylation. The suspension remained stable as f-CNTs remained dispersed even after 24 h. This confirmed that the functionalisation of CNTs using PEGylated phospholipids gives stable formulations. Photographic image of CNTs before and after functionalisation is shown in fig. 1. As seen in the figure, MWCNTs remained settled as such in distilled water before functionalisation, while after functionalisation, f-CNTs could been seen suspended since clear solution was obtained. This further confirms that functionalisation has taken place. Moreover, FT-IR spectrum was recorded and results are shown in fig. 2. The prominent peak in spectra of MWCNTs (fig. 1a) seen at 1400 and 1649 cm−1 may be due to stretching vibrations carbon nanotube backbone. The broad peak at 3426 cm−1 may be due to O–H stretching of the hydroxyl group, which may be due to oscillation of carboxyl groups. These carboxyl groups may be due to partial oxidation of the surfaces of MWCNTs during purification by the manufacturer[30]. The peak at 1721 cm−1 in DSPE-mPEG2000 (fig. 1b) represents the carbonyl bond vibrations, peak at 1100 cm−1 relates to C–O secondary alcohol while at 951 cm−1 represents P–O–C aliphatic stretching vibrations. These peaks seemed to be merged with the CNTs peaks as seen in the f-CNTs spectra (fig. 1c). There may be noncovalent interaction between MWCNTs and DSPE-mPEG2000. Hence, the skeletal vibrations, which were seen in MWCNTs spectra, were also seen in f-CNTs spectra[31].


Gemcitabine hydrochloride-loaded functionalised carbon nanotubes as potential carriers for tumour targeting.

Das S, Desai JL, Thakkar HP - Indian J Pharm Sci (2013)

FT-IR spectrum of MWCNTs.FT-IR spectrum of MWCNTs (a), DSPE-mPEG2000 (b) and f-CNTs (c).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928735&req=5

Figure 2: FT-IR spectrum of MWCNTs.FT-IR spectrum of MWCNTs (a), DSPE-mPEG2000 (b) and f-CNTs (c).
Mentions: The sidewalls of CNTs are highly hydrophobic because of which it is difficult to disperse them both in aqueous and organic media. For the use of CNTs as carriers for drug delivery, it is often necessary to disperse them uniformly in aqueous medium. Hence, functionalisation of CNTs was carried out to impart dispersibility to CNTs in different media. Moreover, for functionalisation PEG was used, which also provides reduced reticuloendothelial system (RES) uptake resulting in prolonged circulation in blood. This property was attributed to the irreversible surface adsorption of PEG molecules on MWCNTs[29]. This surface adsorption was possible by using DSPE, which attaches noncovalently to both CNTs surface and PEG molecules. Hence, DSPE-mPEG2000 was used for functionalisation of MWCNTs in ratio of 1:2 w/w of DSPE:mPEG2000. Different batches prepared with varying ratios of CNTs:DSPE-mPEG2000 revealed that initially particle size of formulation decreased as the amount of DSPE-mPEG2000 increased up to the ratio of 1:2 of CNTs:DSPE-mPEG2000. Further when the amount of DSPE-mPEG2000 was increased, the particle size also increased and reaggregation was observed after 1:4.5 ratio due to presence of excess of DSPE-mPEG2000. Desirable particle size of 178.23 nm (Table 1) was found in ratio of 1:2, hence this CNTs: DSPE-mPEG2000 was taken as optimised ratio and was used for loading of GEM HCl and further characterisation. The f-CNTs had better dispersibility than CNTs because of PEGylation. The suspension remained stable as f-CNTs remained dispersed even after 24 h. This confirmed that the functionalisation of CNTs using PEGylated phospholipids gives stable formulations. Photographic image of CNTs before and after functionalisation is shown in fig. 1. As seen in the figure, MWCNTs remained settled as such in distilled water before functionalisation, while after functionalisation, f-CNTs could been seen suspended since clear solution was obtained. This further confirms that functionalisation has taken place. Moreover, FT-IR spectrum was recorded and results are shown in fig. 2. The prominent peak in spectra of MWCNTs (fig. 1a) seen at 1400 and 1649 cm−1 may be due to stretching vibrations carbon nanotube backbone. The broad peak at 3426 cm−1 may be due to O–H stretching of the hydroxyl group, which may be due to oscillation of carboxyl groups. These carboxyl groups may be due to partial oxidation of the surfaces of MWCNTs during purification by the manufacturer[30]. The peak at 1721 cm−1 in DSPE-mPEG2000 (fig. 1b) represents the carbonyl bond vibrations, peak at 1100 cm−1 relates to C–O secondary alcohol while at 951 cm−1 represents P–O–C aliphatic stretching vibrations. These peaks seemed to be merged with the CNTs peaks as seen in the f-CNTs spectra (fig. 1c). There may be noncovalent interaction between MWCNTs and DSPE-mPEG2000. Hence, the skeletal vibrations, which were seen in MWCNTs spectra, were also seen in f-CNTs spectra[31].

Bottom Line: Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern.Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride.Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.

View Article: PubMed Central - PubMed

Affiliation: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara-390 001, India.

ABSTRACT
The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of -10-1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.

No MeSH data available.


Related in: MedlinePlus