Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric Nanoparticles and their Potential Application as a Treatment for GlioblastomaCastañeda-Gill JM1, Ranjan AP2 and Vishwanatha JK2*
- *Corresponding Author:
- Jamboor K Vishwanatha
Institute for Molecular Medicine and Institute for Cancer Research
University of North Texas Health Science Center
Fort Worth, TX 76107, USA
E-mail: [email protected]
Received date: July 13, 2017; Accepted date: July 24, 2017; Published date: July 31, 2017
Citation: Castañeda-Gill JM, Ranjan AP, Vishwanatha JK (2017) Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric Nanoparticles and their Potential Application as a Treatment for Glioblastoma. J Nanomed Nanotechnol 8: 449. doi: 10.4172/2157-7439.1000449
Copyright: © 2017 Castañeda-Gill JM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from astrocytes located within the cerebrum, resulting in poor prognosis and survival rates following an accepted treatment regimen of surgery, radiation, and temozolomide. Thus, development of new therapeutics is necessary. During the last two decades, methylene blue (MB) has received increased attention as a potential neurotherapeutic due to its duality in brain cancers and neurodegenerative diseases. While MB is capable of easily permeating the blood-brain barrier, its therapeutic concentrations in GBM are known to induce off-target cytotoxicity and thus, another mode of drug delivery must be considered. To this end, encapsulation of formerly unusable compounds into nanoparticles (NPs) made from the biodegradable/biocompatible, FDA approved co-polymer poly(lactide-co-glycolide) (PLGA) has been more commonplace when developing novel therapeutics. In this study, we formulated and characterized Pluronic F68-coated PLGA NPs containing a sodium oleate conjugate of MB (MBOS) via solvent displacement. Conjugation of sodium oleate to MB was shown to reduce its release from PLGA NPs compared to unmodified MB, leading to potential improvements in drug accumulation and therapeutic effectiveness. Our drug-loaded NP preparations, which were ~170 nm in size and had drug loading values of ~2%, were shown to reduce cell viability and cell compartment-specific, as well as overall cell, functions equivalently, if not more so, when compared to free drug in two GBM cell lines. Following bio-distribution analysis of free MBOS compared to its nano-encapsulated counterpart, drug-loaded NPs were shown to more effectively permeate the BBB, which could lead to improvements in therapeutic effectiveness upon further examination in a tumor-bearing mouse model. Based on these results, we believe that the further development and eventual utilization of this nanoformulation could lead to an effective GBM therapy that could extend patient survival rates.