[Journal of Drug Delivery] Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Pla
Phospholipid-based deformable nanovesicles (DNVs) that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol). AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs) or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.
Naren Subbiah,1,2 Jesus Campagna,1 Patricia Spilman,1 Mohammad Parvez Alam,1 Shivani Sharma,3 Akishige Hokugo,4 Ichiro Nishimura,2 and Varghese John1 1Drug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA 2Weintraub Center for Reconstructive Biotechnology, School of Dentistry, University of California, Los Angeles, CA, USA 3California NanoSystems Institute, University of California, Los Angeles, CA, USA 4Regenerative Bioengineering and Repair Laboratory, Department of Surgery, University of California, Los Angeles, CA, USA
Correspondence should be addressed to Varghese John
Received 6 January 2017; Accepted 13 March 2017; Published 5 April 2017
Academic Editor: A. Fadda
Copyright © 2017 Naren Subbiah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.