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      Silicon Nanotubes as Potential Therapeutic Platforms

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          Abstract

          Silicon nanotubes (SiNTs) with unique well-defined structural morphologies have been successfully fabricated and recognized as a novel architecture in the nanoscale Si family. While the typical dendritic microstructure of mesoporous silicon prepared anodically has been exploited previously for therapeutics and biosensing, our status of utilizing SiNTs in this regard is still in its infancy. In this review, we focus on the fundamental properties of such nanotubes relevant to therapeutic applications, beginning with a description of our ability to sensitively tune the structure of a given SiNT through synthetic control and the associated detailed in vitro dissolution behavior (reflecting biodegradability). Emphasis is also placed here on the range of functional moieties available to attach to the surface of SiNTs through a summary of current studies involving surface functionalization and strategies that facilitate conjugation with molecules of interest for multiple purposes, including cell labeling, nucleotide attachment, and scaffolding of therapeutic metallic nanoparticles. Experiments addressing our ability to load the interior of a given nanotube with species capable of providing magnetic field-assisted drug delivery are also briefly described. Given the range of diverse properties demonstrated to date, we believe the future to be quite promising for employing SiNTs as therapeutic platforms.

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          Most cited references52

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          Progress and prospects: immune responses to viral vectors.

          Viral vectors are potent gene delivery platforms used for the treatment of genetic and acquired diseases. However, just as viruses have evolved to infect cells efficiently, the immune system has evolved to fight off what it perceives as invading pathogens. Therefore, innate immunity and antigen-specific adaptive immune responses against vector-derived antigens reduce the efficacy and stability of in vivo gene transfer. In addition, a number of vectors are derived from parent viruses that humans encounter through natural infection, resulting in preexisting antibodies and possibly in memory responses against vector antigens. Similarly, antibody and T-cell responses may be directed against therapeutic gene products that often differ from the endogenous nonfunctional or absent protein that is being replaced. As details and mechanisms of such immune reactions are uncovered, novel strategies are being developed, and vectors are being specifically engineered to avoid, suppress or manipulate the response, ideally resulting in sustained expression and immune tolerance to the transgene product. This review provides a summary of our current knowledge of the interactions between the immune system adeno-associated virus, adenoviral and lentiviral vectors, and their transgene products.
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            Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.

            In preclinical studies, a doxorubicin liposome formulation containing polyethylene-glycol (Doxil) shows a long circulation time in plasma, enhanced accumulation in murine tumors, and a superior therapeutic activity over free (unencapsulated) doxorubicin (DOX). The purpose of this study was to characterize the pharmacokinetics of Doxil in cancer patients in comparison with free DOX and examine its accumulation in malignant effusions. The pharmacokinetics of doxorubicin and/or liposome-associated doxorubicin were analyzed in seven patients after injections of equivalent doses of free DOX and Doxil and in an additional group of nine patients after injection of Doxil only. Two dose levels were examined, 25 and 50 mg/m2. When possible, drug levels were also measured in malignant effusions. The plasma elimination of Doxil followed a biexponential curve with half-lives of 2 and 45 h (median values), most of the dose being cleared from plasma under the longer half-life. Nearly 100% of the drug detected in plasma after Doxil injection was in liposome-encapsulated form. A slow plasma clearance (0.1 liter/h for Doxil versus 45 liters/h for free DOX) and a small volume of distribution (4 liters for Doxil versus 254 liters for free DOX) are characteristic of Doxil. Doxorubicin metabolites were detected in the urine of Doxil-treated patients with a pattern similar to that reported for free DOX, although the overall urinary excretion of drug and metabolites was significantly reduced. Doxil treatment resulted in a 4- to 16-fold enhancement of drug levels in malignant effusions, peaking between 3 to 7 days after injection. Stomatitis related to Doxil occurred in 5 of 15 evaluable patients and appears to be the most significant side effect in heavily pretreated patients. The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier. The enhanced drug accumulation in malignant effusions is apparently related to liposome longevity in circulation. Further clinical investigation is needed to establish the relevance of these findings with regard to the ability of liposomes to modify the delivery of doxorubicin to solid tumors and its pattern of antitumor activity.
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              Porous silicon in drug delivery devices and materials.

              Porous Si exhibits a number of properties that make it an attractive material for controlled drug delivery applications: The electrochemical synthesis allows construction of tailored pore sizes and volumes that are controllable from the scale of microns to nanometers; a number of convenient chemistries exist for the modification of porous Si surfaces that can be used to control the amount, identity, and in vivo release rate of drug payloads and the resorption rate of the porous host matrix; the material can be used as a template for organic and biopolymers, to prepare composites with a designed nanostructure; and finally, the optical properties of photonic structures prepared from this material provide a self-reporting feature that can be monitored in vivo. This paper reviews the preparation, chemistry, and properties of electrochemically prepared porous Si or SiO2 hosts relevant to drug delivery applications.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                01 November 2019
                November 2019
                : 11
                : 11
                : 571
                Affiliations
                Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, TX 76129, USA; nguyen.t.le@ 123456tcu.edu (N.T.L.); Yuan.tian@ 123456tcu.edu (Y.T.); R.gonzalezrodriguez@ 123456tcu.edu (R.G.-R.)
                Author notes
                [* ]Correspondence: j.coffer@ 123456tcu.edu ; Tel.: +01-817-257-6223
                Article
                pharmaceutics-11-00571
                10.3390/pharmaceutics11110571
                6920902
                31683869
                3a414852-cf1c-4608-ac16-912d2d2351e4
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 September 2019
                : 28 October 2019
                Categories
                Review

                silicon nanotubes,surface chemistry,drug delivery
                silicon nanotubes, surface chemistry, drug delivery

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