Cationic solid lipid nanoparticles loaded by cysteine proteinase genes as a novel anti-leishmaniasis DNA vaccine delivery system: characterization and in vitro evaluations
| Autor: | Alireza Vatanara, Abdolhossein Rouholamini Najafabadi, Elham Gholami, Sima Rafati, Delaram Doroud, Rouhollah Vahabpour, Farnaz Zahedifard |
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| Přispěvatelé: | Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), School of Pharmacy [TUMS, Teheran, Iran], Tehran University of Medical Sciences (TUMS), D. Doroud thanks Pasteur Institute of Iran and Tehran University of Medical sciences for supporting her PhD studentship., The authors thank Dr. M. Amanzadeh, Cell Bank of Pasteur Institute of Iran, for his advice and guidance on the MTT assay and Dr. A. Saadat and Dr. E. Moazeni, Pharmaceutics Dept., Faculty of Pharmacy, Tehran University of Medical Sciences, for their technical support on size and zeta potential determinations. We are also grateful for English revision by Amir Mizbani, D. Doroud thanks Pasteur Institute of Iran and Tehran University of Medical Sciences for Supporting her PhD studentship., The authors thank Dr. M. Amanzadeh, Cell Bank Dept., Pasteur Institute of Iran, for his advice and guidance on the MTT assay. |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Cystein proteinase
Drug Evaluation Preclinical lcsh:RS1-441 Pharmaceutical Science Tetrazolium Salts 02 engineering and technology MESH: Dogs chemistry.chemical_compound 0302 clinical medicine Drug Delivery Systems Cysteine Proteases Chlorocebus aethiops Zeta potential Vaccines DNA MESH: Animals 030212 general & internal medicine Cytotoxicity Leishmaniasis 0303 health sciences MESH: Vaccines DNA/administration & dosage Cetyl palmitate Formazans MESH: Nanoparticles*/administration & dosage Transfection MESH: Tetrazolium Salts 021001 nanoscience & nanotechnology Lipids 3. Good health MESH: COS Cells MESH: Cysteine Proteases/genetics Biochemistry MESH: Cysteine Proteases/metabolism COS Cells MESH: Drug Evaluation Preclinical Delivery system 0210 nano-technology Plasmids Cell Survival Green Fluorescent Proteins Heterologous MESH: Leishmaniasis/metabolism Biology DNA vaccination lcsh:Pharmacy and materia medica Excipients 03 medical and health sciences Dogs MESH: Leishmaniasis/prevention & control MESH: Plasmids Cations Solid lipid nanoparticle medicine Animals MESH: Particle Size Particle Size MESH: Formazans MESH: Cations Gene Leishmaniasis Vaccines 030304 developmental biology MESH: Excipients Pharmacology MESH: Transfection lcsh:RM1-950 Cationic polymerization MESH: Green Fluorescent Proteins/genetics MESH: Nanoparticles*/analysis medicine.disease Virology MESH: Lipids MESH: Cercopithecus aethiops In vitro MESH: Leishmaniasis Vaccines/administration & dosage lcsh:Therapeutics. Pharmacology chemistry Nanoparticles [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology MESH: Drug Delivery Systems MESH: Cell Survival/drug effects MESH: Nanoparticles |
| Zdroj: | Journal of Pharmacy and Pharmaceutical Sciences Journal of Pharmacy and Pharmaceutical Sciences, Canadian Society for Pharmaceutical Sciences, 2010, 13 (3), pp.320-335. ⟨10.18433/J3R30T⟩ Journal of Controlled Release Journal of Controlled Release, Elsevier, 2010, 148 (1), pp.e105-106. ⟨10.1016/j.jconrel.2010.07.079⟩ Scopus-Elsevier Journal of Pharmacy & Pharmaceutical Sciences, Vol 13, Iss 3 (2010) |
| ISSN: | 1482-1826 0168-3659 |
| DOI: | 10.18433/J3R30T⟩ |
| Popis: | Purpose: Leishmaniasis is a major health problem in many tropical and sub-tropical countries and development of a safe and easily-available vaccine has high priority. Although several antigens potentially capable of inducing protective immunity have been studied, in the absence of pharmaceutical industry interest they have remained as fine publications only. Amongst them, Cathepsin L-like cysteine proteinases (CPs) have received considerable attention and type I and II CPs have been used in a heterologous prime-boost vaccination regime for experimental visceral leishmaniasis in dogs. Due to the promising results of the mentioned vaccination regime, we aimed to evaluate cationic solid lipid nanoparticles (cSLNs) for in vitro delivery of cpa, cpb and cpbCTE intended to be used as a cocktail DNA vaccine in our forthcoming studies. Methods: cSLNs were formulated of cetyl palmitate, cholesterol, DOTAP and Tween 80 via melt emulsification method followed by high shear homogenization. Different formulations were prepared by anchoring pDNAs on the surface of cSLNs via charge interaction. The formulations were characterized according to their size and zeta potential as well as pDNA integrity and stability against DNase I treatment. Lipoplexes' cytotoxicity was investigated on COS-7 cells by MTT test. The effect of the DOTAP:pDNA ratio on protection ability and cytotoxicity was also studied. In vitro transfection efficiency was qualified by florescent microscopy and quantified using flow cytometry technique. Results: cSLN-pDNA complexes were formulated with suitable size and zeta potential. Efficiency/cytotoxicity ratio of cSLN-pDNAs formulations was comparable to linear PEI-25KD-pDNAs polyplexes while exhibiting significantly lower cytotoxicity. Conclusion: Tested formulations were able to deliver immunogenic CP genes efficiently. This data proves the ability of this system as a promising DNA vaccine carrier for leishmaniasis to cover the main drawback of naked pDNA delivery that is rapid elimination from the circulation. |
| Databáze: | OpenAIRE |
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