Drug Designing: Open Access
Open Access
ISSN: 2169-0138
ISSN: 2169-0138
Kriti Soni and Kanchan Kohli
Jamia Hamdard, India
Posters & Accepted Abstracts: Drug Des
Statement of the Problem: The rationale of using sulforaphane, a naturally occurring isothiocyanate, with gold nanoparticles is that the chemical moiety present in sulforaphane efficiently binds with the surface of gold nanoparticles. Gold nanoparticles are known to be passively up taken by cancer cells and lead to cytotoxic effect on them and sulforaphane has been found to be effective in cancer treatment thus the conjugated particles have enhanced anticancer effect without affecting the normal cells. Methodology & Theoretical Orientation: Sulforaphane was extracted from commercially available broccoli and broccoli sprouts. Electrolysis was done for 15 minutes at 30V. The formulations were then made to undergo 14 homogenization cycles at 1000 bar pressure. This was optimized using design expert software version 9.0.1. Simulations were performed and resultant structure was obtained using simulation software Quntumwise ATK and band structure thus produced was obtained. Particle size distribution and zeta potential were measured by dynamic light scattering (DLS) technique using Zetasizer, (Nano-ZS, and Malvern Instruments) and analyzed by â�?�?DTS nanoâ�?�? software. The in vitro release study of the gold nanoparticle conjugates of SFN and SFN suspension was performed in phosphate buffer solution (PBS) by using a dialysis bag with molecular weight cut-off 12000kDa (Sigma Aldrich). Surface morphology and size of the formulation was observed under transmission electron microscope (JOEL 2100F) operating at 200 kV at All India Institute of Medical Sciences. DSC (Pyris 6 DSC, Perkin Elmer Software Pyris series) study was carried out over a temperature range of 35â�?�?400�?ºC. FT-IR Spectroscopic (Shimadzu, Japan) studies of the samples were carried out by appropriately diluting the sample (1:100) with dried potassium bromide. The stability studies of the nanoparticle were carried out as per the guidelines given in the ICH Q1A (R2) (ICH topic Q1 A (R2) 2009) in Thermo lab TH 90S. The animal study was conducted according to the protocol No.1067 approved by Institutional Animal Ethical Care Committee (IAEC) of Jamia Hamdard University, India. The amount of the drug permeated was determined by using the HPLC method. Inductively coupled plasma mass spectrometry (ICP-MS) was done to analyze the gold content of the formulations. Laser Confocal Microscope with Fluorescence Correlation Spectroscopy (FCS) - Olympus FluoViewâ�?¢ FV1000 using software Olympus fluoview ver.1.7a was done. The comparative in-vivo pharmacokinetic studies were carried out and analyzed by the established HPLC method. An MTT assay was used to assess the cytotoxicity was done on Caco-2 cells (ATCC, USA grown in Dabur Research Foundation, Sahibabad) and other carcinoma cell lines. Findings: DSC data confirms that drug has been incorporated with gold nanoparticles. Confocal studies reveal that the extent of permeation of sulforaphane conjugated gold nanoparticles i. e. SGnp has shown an increase in permeation. Particle size measurement of simple gold NP before loading drug was measured and confirmed on TEM also. FTIR data reveals linking between drug and gold nanoparticles. In vitro drug release kinetics showed that both formulations showed release profile showing first order release. Stability studies revealed stable formulations. MTT assays reveal that the formulations have cytotoxicity of more than 80% at 48 hours. The pharmacokinetic data revealed that the SGnp enhanced oral bioavailability as compared to plain sulforaphane. Conclusion & Significance: It can thus be concluded that gold nanoparticles gives an added advantage of greater stability, more cytotoxicity towards cancer cells and enhanced permeation through GIT. The cytotoxic potential of sulforaphane was supplemented by gold nanoparticles. It was found to increase the permeation through gut and better kinetics profile. It was found to be stable for a considerable period of time and cell line studies further confirmed the cytotoxicity of the formulation which will ultimately cause cell death in cancer cells.
Kriti Soni is currently a PhD research scholar in Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, India. She possesses hands on experience and knowledge of laboratory skills. She has been awarded the Best Poster Award for her research entitled “Lipid Drug Conjugated Nanoparticles for Oral Delivery of an Anti-foliate Drug” at 5th International Conference and Exhibition on Pharmaceutics and Novel Drug Delivery Systems at Dubai, UAE and is a winner of several awards for best posters at national conferences also.
Email: sonikriti20@yahoo.in