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Formulation of a Sustained Release Docetaxel Loaded Cockle Shell-Derived Calcium Carbonate Nanoparticles against Breast Cancer

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Abstract

Purpose

Here, we explored the formulation of a calcium carbonate nanoparticle delivery system aimed at enhancing docetaxel (DTX) release in breast cancer.

Methods

The designed nano- anticancer formulation was characterized thorough X-ray diffraction (XRD), Fourier transformed infrared (FTIR), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) and Brunauer-Emmett-Teller (BET) methods. The nano- anticancer formulation (DTX- CaCO3NP) was evaluated for drug delivery properties thorough in vitro release study in human body simulated solution at pH 7.4 and intracellular lysosomal pH 4.8.

Results

Characterization revealed the successful synthesis of DTX- CaCO3NP, which had a sustained release at pH 7.4. TEM showed uniformly distributed pleomorphic shaped pure aragonite particles. The highest entrapment efficiency (96%) and loading content (11.5%) were obtained at docetaxel to nanoparticles ratio of 1:4. The XRD patterns revealed strong crystallizations in all the nanoparticles formulation, while FTIR showed chemical interactions between the drug and nanoparticles with negligible positional shift in the peaks before and after DTX loading. BET analysis showed similar isotherms before and after DTX loading. The designed DTX- CaCO3NP had lower (p < 0.05) cytotoxity against MCF-7 cells than DTX at 24 h but comparable (p > 0.05) effects at 48 h and 72 h. However, the DTX- CaCO3NP released less than 80% of bond DTX at 48 and 72 h but showed comparable effects with free DTX.

Conclusions

The results showed that the developed DTX- CaCO3NP released DTX slower at pH 7.4 and had comparable cytotoxicity with free DTX at 48 and 72 h in MCF-7 cells.

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Abbreviations

BET:

Brunauer-Emmett-Teller

CaCO3 :

Calcium carbonate

CaCO3NP:

Calcium carbonate nanoparticle

DMSO:

Dimethylsulfoxide

DTX:

Docetaxel

DTX- CaCO3NP:

Docetaxel calcium carbonate nanoparticle formulation

EE:

Encapsulation efficiency

FESEM:

Field emission scanning electron microscopy

FTIR:

Fourier transformed infrared

MTT:

3-[4, 5- dimethylthiazol-2-yl]-3, 5-diphenyl tetrazolium bromide dye

NP:

Nanoparticle

RPMI:

Rosewell park memorial institute medium

TEM:

Transmission electron microscopy

XRD:

X-ray diffraction

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Acknowledgments and Disclosures

The authors are grateful for funding from Universiti Putra Malaysia Postgraduate Grant Scheme, (GP/ IPS/ 2014/ 9,440,300). The authors declare no conflict of interest.

Data Availability

All raw data are available on request from Dr. NIH.

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Correspondence to Nahidah Ibrahim Hammadi or Md Zuki Abu Bakar Zakaria.

Additional information

Nahidah Ibrahim Hammadi, Yusuf Abba, Mohd Noor Mohd Hezmee, Intan Shameha Abdul Razak, Alhaji Zubair Jaji, Tijani Isa, Saffanah Khuder Mahmood, MD Zuki Abu Bakar Zakaria contributed equally to the manuscript and have read and approved the final manuscript.

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Hammadi, N.I., Abba, Y., Hezmee, M.N.M. et al. Formulation of a Sustained Release Docetaxel Loaded Cockle Shell-Derived Calcium Carbonate Nanoparticles against Breast Cancer. Pharm Res 34, 1193–1203 (2017). https://doi.org/10.1007/s11095-017-2135-1

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  • DOI: https://doi.org/10.1007/s11095-017-2135-1

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