Development and Evaluation Of Chemodrug-Loaded Albumin Polymeric Nanocarriers for the Treatment of Neuroblastoma
Arun Kotha1, Sushrut Marathe1, Rohit Joshi1, André S. Bachmann2, Mahavir B. Chougule1,3*
1Translational Bio-pharma Engineering Nanodelivery Research Laboratory, Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, MS
2Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI
3The Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, Oxford, MS
Neuroblastoma is a most common type of extracranial solid tumor in children. Poor survival rates and adverse side effects of existing therapies necessitates the need for novel and target specific delivery systems. Nanocarriers can provide a means for delivery of drugs by taking advantage of the EPR effect, with decreased dose and reduced toxicity. Sulfasalazine has recently been identified to inhibit the cell growth in neuroblastoma cells. Therefore, the objective of our study was to formulate the sulfasalazine loaded albumin-chitosan hybrid nanocarriers with particle size less than 100 nm and evaluate them against neuroblastoma cells which can be administered systemically to effectively overcome the challenges posed by the drug. In this study, we developed a nano-precipitation method to produce the self-assembling Sulfasalazine-loaded Bovine Serum Albumin (BSA) nanocarriers. The experiments were designed using the Taguchi orthogonal array. The nanocarriers were PEGylated using the activated mPEG-SPA. The nanocarriers were characterized by using dynamic light scattering particle size analysis and zeta potential analysis. The drug release study in a simulated body fluid of pH 7.4 was performed to evaluate the release profile of the drug from the nanocarriers. Results showed that the Sulfasalazine-loaded PEGylated nanocarriers had an average particle size of 80.556 ± 3.119 nm with an average PDI of 0.120 ± 0.037 and zeta potential of the formulation was found to be 5.593 ± 0.583mV. The entrapment efficiency of the formulation was found to be 98.65%. The achieved drug loading for the final formulation was about 6.78% (w/w). In the release study, the developed nanocarriers showed the controlled release of the drug up to 48 h in a simulated body fluid of pH 7.4. The nanocarriers were found to be stable in the presence of PBS 7.4 and 55% FBS solution for more than 72 h. Currently, the developed nanocarriers are being tested for dose-dependent anticancer effects against neuroblastoma cell lines. We produced stable Sulfasalazine-loaded nanocarriers which showed controlled release of the loaded drug. This investigation infers that albumin-chitosan polymer-based nanocarriers are useful for the delivery of anticancer drugs. The results for the prepared formulation are encouraging and suggest further analysis of these nanocarriers by in vitro studies in cancer cells and in vivo studies using neuroblastoma tumor-bearing mice.