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Supercritical Fluid Technology-Based Trans-Resveratrol SLN for Long Circulation and Improved Radioprotection

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Abstract

Purpose

To alleviate the harmful effects of radiations during occupational radiology, radiotherapy and diagnosis, radioprotective system with lower toxicity and extended activity is imperative. Trans-resveratrol (RVL) acts through free radical scavenging/antioxidant mechanism to mitigate the radiation-induced damage. But, its poor solubility and fast metabolism impede its efficacy. Thus, encapsulation of RVL into long circulating solid lipid nanoparticle (SLN) is aimed.

Method

Supercritical CO2 solution of RVL, Gelucire®50/02 and Gelucire®50/13 SLN, was rapidly expanded into aqueous phase containing Tween 80, sonicated and lyophilized to get SLN. Particle size, polydispersity index (PDI), entrapment efficiency (%EE), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), drug release, in vivo pharmacokinetics, antioxidant assays, radiation-induced lipid peroxidation and plasmid DNA relaxation assays were studied. Stability studies were performed to analyze drug degradation and shelf life.

Results

Optimized formulation (F9) had %yield, particle size, PDI, %EE and %drug release (after 72 h) of 68.48 ± 5.73 %, 276.7 ± 5.33 nm, 0.18 ± 0.032, 62.66 ± 4.52 % and 70.05 ± 3.003 %, respectively. Electron microscopy revealed nearly spherical particles, while DSC and XRD showed reduced crystalline peaks. F9 showed higher AUC and sustained release of RVL in rats (i.v. bolus) and increased antioxidant activities and radioprotection as compared to RVL solution. Shelf life of >2 years was predicted for F9 (at 8 °C).

Conclusion

Results are encouraging to use F9 for radiation exposure prophylaxis.

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Abbreviations

%EE:

Entrapment efficiency

%IDD:

Percentage inhibition of 2-deoxy-d-ribose degradation

%IDPPH:

Percentage DPPH scavenging activity

%ILPO:

Percent inhibition of lipid peroxidation

%SOR:

Superoxide radical scavenging activity

AA:

Antioxidant activity

CO2 :

Carbon dioxide

DNA:

Deoxyribonucleic acid

DPPH:

1,1-Diphenyl-2-Picryl-Hydrazyl Free Radical

DSC:

Differential scanning calorimetry

IDV:

Integrated density values

ICH:

International Council for Harmonisation

NBT:

Nitro blue tetrazolium

OI:

Oxidation index

PDI:

Polydispersity Index

PEG:

Polyethylene glycol

PMS-NADH:

Phenazine methoxy sulphate nicotinamide adenine dinucleotide

RESS:

Rapid expansion of supercritical fluid

RVL:

Trans-resveratrol

SCF:

Supercritical fluid

SEM:

Scanning electron microscopy

SLNs:

Solid lipid nanoparticles

TEM:

Transmission electron microscopy

XRD:

X-ray diffraction

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Acknowledgments

The first author acknowledges the University Grants Commission, New Delhi, India, for the financial support under the Special Assistance Program (SAP-II, 3-58/2011).

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Authors and Affiliations

  1. Nanomedicine Research Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India

    Iqbal Ahmad, Mohammed Anwar, Sohail Akhter, Asgar Ali & Farhan Jalees Ahmad

  2. LE STUDIUM®, Centre de Biophysique Moléculaire (CBM)-CNRS UPR 4301, rue Charles Sadron, 45071, Orléans Cedex 2, France

    Sohail Akhter

  3. Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, DRDO, New Delhi, India

    Pallavi Thakur, Raman Chawla & Rakesh Kumar Sharma

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  1. Iqbal Ahmad
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Correspondence to Iqbal Ahmad or Farhan Jalees Ahmad.

Ethics declarations

In vivo pharmacokinetic study was performed after proper authorization from Institutional Animal Ethics Committee, Jamia Hamdard, New Delhi, and strict guidelines of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA, Ministry of Culture, and Government of India) were followed.

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The authors declare that they have no conflicts of interest.

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Ahmad, I., Anwar, M., Akhter, S. et al. Supercritical Fluid Technology-Based Trans-Resveratrol SLN for Long Circulation and Improved Radioprotection. J Pharm Innov 11, 308–322 (2016). https://doi.org/10.1007/s12247-016-9254-9

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