Celia C.,Methodist Hospital Research Institute |
Celia C.,University of Catanzaro |
Ferrati S.,Methodist Hospital Research Institute |
Bansal S.,Methodist Hospital Research Institute |
And 12 more authors.
Advanced Healthcare Materials | Year: 2014
Metronomic chemotherapy supports the idea that long-term, sustained, constant administration of chemotherapeutics, currently not achievable, could be effective against numerous cancers. Particularly appealing are liposomal formulations, used to solubilize hydrophobic therapeutics and minimize side effects, while extending drug circulation time and enabling passive targeting. As liposome alone cannot survive in circulation beyond 48 h, sustaining their constant plasma level for many days is a challenge. To address this, we develop, as a proof of concept, an implantable nanochannel delivery system and ultra-stable PEGylated lapatinib-loaded liposomes, and we demonstrate the release of intact vesicles for over 18 d. Further, we investigate intravasation kinetics of subcutaneously delivered liposomes and verify their biological activity post nanochannel release on BT474 breast cancer cells. The key innovation of this work is the combination of two nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as passive-targeting vectors and nanofluidics to maintain therapeutic constant plasma levels. In principle, this approach could maximize efficacy of metronomic treatments. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Sih J.,Methodist Hospital Research Institute |
Bansal S.S.,Methodist Hospital Research Institute |
Filipini S.,Methodist Hospital Research Institute |
Ferrati S.,Methodist Hospital Research Institute |
And 9 more authors.
Analytical and Bioanalytical Chemistry | Year: 2013
Novel drug delivery systems capable of continuous sustained release of therapeutics have been studied extensively for use in the prevention and management of chronic diseases. The use of these systems holds promise as a means to achieve higher patient compliance while improving therapeutic index and reducing systemic toxicity. In this work, an implantable nanochannel drug delivery system (nDS) is characterized and evaluated for the long-term sustained release of atorvastatin (ATS) and trans-resveratrol (t-RES), compounds with a proven role in managing atherogenic dyslipidemia and promoting cardioprotection. The primary mediators of drug release in the nDS are nanofluidic membranes with hundreds of thousands of nanochannels (up to 100,000/mm2) that attain zero-order release kinetics by exploiting nanoconfinement and molecule-to-surface interactions that dominate diffusive transport at the nanoscale. These membranes were characterized using gas flow analysis, acetone diffusion, and scanning and transmission electron microscopy (SEM, TEM). The surface properties of the dielectric materials lining the nanochannels, SiO 2 and low-stress silicon nitride, were further investigated using surface charge analysis. Continuous, sustained in vitro release for both ATS and t-RES was established for durations exceeding 1 month. Finally, the influence of the membranes on cell viability was assessed using human microvascular endothelial cells. Morphology changes and adhesion to the surface were analyzed using SEM, while an MTT proliferation assay was used to determine the cell viability. The nanochannel delivery approach, here demonstrated in vitro, not only possesses all requirements for large-scale high-yield industrial fabrication, but also presents the key components for a rapid clinical translation as an implantable delivery system for the sustained administration of cardioprotectants. © 2012 Springer-Verlag Berlin Heidelberg.
Grattoni A.,Methodist Hospital Research Institute |
Fine D.,Methodist Hospital Research Institute |
Zabre E.,Methodist Hospital Research Institute |
Ziemys A.,Methodist Hospital Research Institute |
And 10 more authors.
ACS Nano | Year: 2011
Nanoparticles and their derivatives have engendered significant recent interest. Despite considerable advances in nanofluidic physics, control over nanoparticle diffusive transport, requisite for a host of innovative applications, has yet to be demonstrated. In this study, we performed diffusion experiments for negatively and positively charged fullerene derivatives (dendritic fullerene-1, DF-1, and amino fullerene, AC60) in 5.7 and 13 nm silicon nanochannels in solutions with different ionic strengths. With DF-1, we demonstrated a gated diffusion whereby precise and reproducible control of the dynamics of the release profile was achieved by tuning the gradient of the ionic strength within the nanochannels. With AC60, we observed a near-surface diffusive transport that produced release rates that were independent of the size of the nanochannels within the range of our experiments. Finally, through theoretical analysis we were able to elucidate the relative importance of physical nanoconfinement, electrostatic interactions, and ionic strength heterogeneity with respect to these gated and near-surface diffusive transport phenomena. These results are significant for multiple applications, including the controlled administration of targeted nanovectors for therapeutics. © 2011 American Chemical Society.
Grattoni A.,University of Texas Health Science Center at Houston |
Fine D.,University of Texas Health Science Center at Houston |
Ziemys A.,University of Texas Health Science Center at Houston |
Gill J.,University of Texas Health Science Center at Houston |
And 5 more authors.
Current Pharmaceutical Biotechnology | Year: 2010
Significant recent progress has been made in the development of microfabricated nanofluidic devices for use in the biomedical sciences. Novel nanotechnological approaches have been explored in view of a more individualized medical approach. Much of the development has been fuelled by the advantages derived from utilizing nanoscale phenomena to manipulate fluid samples or mediate drug delivery. As such, we present a comprehensive review of nanochannel technologies, highlighting their potential for diagnostic and therapeutic applications. © 2010 Bentham Science Publishers Ltd.
Grattoni A.,University of Houston |
Shen H.,University of Houston |
Fine D.,University of Houston |
Ziemys A.,University of Houston |
And 8 more authors.
Pharmaceutical Research | Year: 2011
Purpose: The purpose of this study is to demonstrate the long-term, controlled, zero-order release of low- and high-molecular weight chemotherapeutics through nanochannel membranes by exploiting the molecule-to-surface interactions presented by nanoconfinement. Methods: Silicon membranes were produced with nanochannels of 5, 13 and 20 nm using standardized industrial microfabrication techniques. The study of the diffusion kinetics of interferonα-2b and leuprolide was performed by employing UV diffusion chambers. The released amount in the sink reservoir was monitored by UV absorbance. Results: Continuous zero-order release was demonstrated for interferonα-2b and leuprolide at release rates of 20 and 100 μg/day, respectively. The release rates exhibited by these membranes were verified to be in ranges suitable for human therapeutic applications. Conclusions: Our membranes potentially represent a viable nanotechnological approach for the controlled administration of chemotherapeutics intended to improve the therapeutic efficacy of treatment and reduce many of the side effects associated with conventional drug administration. © 2010 Springer Science+Business Media, LLC.
Bruno G.,Houston Methodist Research Institute HMRI |
Bruno G.,Polytechnic University of Turin |
Geninatti T.,Houston Methodist Research Institute HMRI |
Geninatti T.,University of Chinese Academy of Sciences |
And 7 more authors.
Nanoscale | Year: 2015
General adoption of advanced treatment protocols such as chronotherapy will hinge on progress in drug delivery technologies that provide precise temporal control of therapeutic release. Such innovation is also crucial to future medicine approaches such as telemedicine. Here we present a nanofluidic membrane technology capable of achieving active and tunable control of molecular transport through nanofluidic channels. Control was achieved through application of an electric field between two platinum electrodes positioned on either surface of a 5.7 nm nanochannel membrane designed for zero-order drug delivery. Two electrode configurations were tested: laser-cut foils and electron beam deposited thin-films, configurations capable of operating at low voltage (≤1.5 V), and power (100 nW). Temporal, reproducible tuning and interruption of dendritic fullerene 1 (DF-1) transport was demonstrated over multi-day release experiments. Conductance tests showed limiting currents in the low applied potential range, implying ionic concentration polarization (ICP) at the interface between the membrane's micro- and nanochannels, even in concentrated solutions (≤1 M NaCl). The ability of this nanotechnology platform to facilitate controlled delivery of molecules and particles has broad applicability to next-generation therapeutics for numerous pathologies, including autoimmune diseases, circadian dysfunction, pain, and stress, among others. This journal is © The Royal Society of Chemistry 2015.
NanoMedical Systems | Date: 2011-05-19
A nano-scale device and method of manufacturing and use. The nano-scale device may be used in-vivo and may comprise a fluid path with an inlet microchannel, an outlet microchannel, and a nanochannel. The fluid path comprises bio-robust material. In certain embodiments, the bio-robust material may be coated over a material that is not bio-robust.
NanoMedical Systems | Date: 2014-12-09
Devices and methods for long-term sustained release of a fragrant compound. Exemplary embodiments may comprise a channeled member with nanochannels or microchannels to provide a sustained release of the fragrant compound.
NanoMedical Systems | Date: 2014-08-11
Devices and methods for administering a therapeutic agent, comprising an implantable delivery device. Exemplary embodiments comprise a reservoir in fluid communication with a channeled member, and a compound comprising the therapeutic agent and a solubilizer disposed within the reservoir.