| AVS 63rd International Symposium & Exhibition | |
| Nanometer-scale Science and Technology | Tuesday Sessions |
| Session NS-TuP |
| Session: | Nanometer-scale Science & Technology Poster Session |
| Presenter: | Carlos Serna, The University of Texas at El Paso |
| Authors: | C. Serna, The University of Texas at El Paso A. Ornleas, The University of Texas at El Paso E. Iniguez, The University of Texas at El Paso K. Michael, The University of Texas at El Paso R. Maldonado, The University of Texas at El Paso T. Boland, The University of Texas at El Paso |
| Correspondent: | Click to Email |
Leishmania major is azoonotic flagellate protozoan transmitted to humans and other mammals through phlebotomine female sand flies. L. major is mainly responsible for causing cutaneous leishmaniasis (CL) in endemic areas of the Old World, with about 1 million new infections each year [1]. The Mannich base compound 1-acetyl-3,5-dibenzylidene-4-piperidone(2) has been found to have effective anti-parasitic properties, but lacks solubility making it difficult to deliver using standard methods. In this study, we synthesized gelatin nanoparticles (GNP) as carriers for the treatment molecule and demonstrate an effective method of delivering anti-parasitic treatment enhancing drug delivery and reducing toxicity in treatment.
Materials and Methods: 1-acetyl-3,5-dibenzylidene-4-piperidone(2) was synthesized by dissolving 3,5-dibenzylidene-4-piperidone(1)in a mixture of 10% acetic anhydride and 5% diisopropylethylamine in dichloromethane while stirring at room temperature. The Ofokansi et al. [2] two-step desolvation method was applied to produce GNP. To maximize the encapsulation yield of the compound, the preparation method was further modified by limiting the drop-wise cross-linking agent (glutaraldehyde) rate to 30 min and replacing DI water with phosphate buffer saline (PBS) for higher pH stability. Unloaded GNP sizes were determined using a particle size analyzer (Nanosight) in order to test for GNP swelling in varying pH levels. UV visible spectroscopy was used to identify the release rate and total concentration of the compound encapsulated. A viability and cytotoxicity assay was conducted in the testing of loaded and unloaded GNP.
Results and Discussion: The mode values of size distributions using PBS pH 5, 7,and 9 in the production of GNP were found to be 73 nm, 91 nm, and 121 nm respectively. Using UV visible spectroscopy, the concentration of compoundencapsulated by the GNP was found to be 4.01 μg/mL released over a time frame of 96 h in 2.4 g of GNP. A viability assay showed an EC50 value of 2.26 μM for 1-acetyl-3,5-dibenzylidene-4-piperidone(2) in L. major; cytotoxicity for the murine intraperitoneal macrophages showed an IC50 value of 6.35 μM.
Conclusions: GNP characterization showed an increase in size with respect to increasing pH in PBS used in the production process; the swelling initiated by exposing GNP produced at pH 5 to a PBS solution of pH 8 showed a release rate of 1 μg/mL per day for 4 days. Viability assays showed the GNP to be effective against L. major when encapsulated and non lethal when lacking a molecule payload.
References:
1. Alrajhi A.A. N Engl J Med. 2002, 346:891-895.
2. Ofokansi K. Eur. J. Pharm. Biopharm. 2010,76,1-9.