Abstract 2197: Mucopenetrating magnetic nanoparticles for drug delivery
Authors: Viajayakumar N. Boya, Renn Lovett, Saini Satua, Vaibhav Gandhi, Prashanth K.B. Nagesh, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu
Journal: Cancer Research (2016)

Abstract Objectives: Cervical cancer (CxCa) is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. However, systemic chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity due to limited concentration of drug reaching to mucosal tissue and blocking of drug penetration through the epithelial mucus surface of the cervix. Mucus in general functions as a protective barrier to for viruses and bacteria, but in cervical cancer condition it poses a serious issue for drug delivery modalities. Therefore, our study was aimed to develop a nanoparticle formulation that can effectively bind and penetrate the mucin barrier of the tissues for effective drug delivery applications. Methods: Iron oxide based magnetic nanoparticles (MNPs) were prepared by precipitation of iron salts in the presence of ammonia with subsequent coating with β-cyclodextrin (β-CD) and/or pluronic polymer (F127). Four different compositions of MNP formulations, plain MNPs, MNPs with β-CD (MNP+βCD), MNPs with F127 (MNP+F127), and MNPs with β-CD and F127 (MNP+βCD-F127) were formulated for this study. Particle size, distribution, and zeta potential of MNPs and MNP-mucin were measured using the Zetasizer based on dynamic light scattering technique, mucin binding ability of MNPs was measured using SpectraMax M2e plate reader, migration of MNPs in the presence of mucin was measured using Boyden chamber assay, and tissue uptake/internalization was measured by Prussian blue staining and fluorescence techniques. Results: Among four different formulations (MNPs, MNPs+βCD, MNP+F127, and MNP+βCD-F127), MNP+βCD-F127 formulation is unique due to its triple layered composition. This MNP formulation was prevented from aggregation in particle size anaysis in solution, indicating its dispersive nature along with penetration compatibility in mucus network. Instantaneous and long term mucin binding experiments suggest that MNP+βCD-F127 nanoparticles strongly interacted with mucin layer. Further, our mucin incubated nanoparticles effectively pass through membrane in Boyden chamber migration assay. Moreover, tissue uptake/internalization studies demonstrated an efficient penetration of MNP+βCD-F127 nanoparticles through mucin layer. Conclusion: All above biophysical properties of MNP+βCD-F127 nanoparticles demonstrate that our unique formulation can bind and penetrate the mucus barrier. This study suggest that this unique nanoparticle formulation could a good candidate for local drug delivery applications for overcoing problems associated with cervical cancer treatment. Citation Format: Viajayakumar N. Boya, Renn Lovett, Saini Satua, Vaibhav Gandhi, Prashanth K.B. Nagesh, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu. Mucopenetrating magnetic nanoparticles for drug delivery. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2197.