Multistage delivery of active agents

Inactive Publication Date: 2008-12-18
BOARD OF RGT THE UNIV OF TEXAS SYST +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, even the best current therapies fa

Method used

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  • Multistage delivery of active agents
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  • Multistage delivery of active agents

Examples

Experimental program
Comparison scheme
Effect test

working example 1

[0137]The following experiments were conducted to study loading and release of selected second stage particles into nanoporous silicon first stage microparticles. Biodegradation and biocompatibility of the nanoporous silicon first stage particles was also studied.

Materials and Methods

Z2 Analysis

[0138]Particles were counted in a Z2 Coulter® Particle Counter and Size Analyzer (Beckman Coulter). The aperture size used for particle analysis was 50 μm. The lower and upper size limits for analysis were set at 1.8 and 3.6 μm. For analysis, particles were suspended in the balanced electrolyte solution of the instrument (ISOTON® II Diluent) and counted. The total volume of original suspension of particles did not exceed 0.3% of the final analysis volume.

Oxidation of Silicon Microparticles

[0139]Silicon microparticles in IPA were dried in a glass beaker kept on a hot plate (80-90° C.). Silicon particles were oxidized in piranha (1 volume H2O2 and 2 volumes of H2SO4). The particles sonicated af...

working example 2

[0216]A multi-stage delivery system based on biodegradable silicon particles containing nanopores of specific size as first stage carriers that may load, carry, release and deliver into cells multiple types of nanoparticles with a precise control was developed. The first stage silicon nanoporous particles may be simultaneously loaded with different types of second stage nanoparticles, which are released in a sustained fashion over time. The major physical, chemical, and electrostatic mechanisms that control the loading and release of second stage nanoparticles were defined. Finally, it was shown that the porous silicon carriers are able to locally delivery the second stage nanoparticles into the cytoplasm. Taken together, these studies provide evidence that silicon nanoporous particles may be used as cargoes for the simultaneous deliver of different types of nanovectors into cells. This system may offer unprecedented methods to achieve intracellular delivery of multiple therapeutics...

working example 3

Liposomes in 3.5 Micron Silicon Particles

[0248]Fluorescently labeled siRNA loaded 1,2-dioleoyl-sn-glycero-3-phosphaticholine (DOPC) liposomes were prepared as detailed in C. N. Landen Jr., et al. Cancer Res. 2005, 65(15), 6910-6918, and J. Clin. Cancer Res. 2006; 12(16), 4916-4924.

[0249]Fluorescently labeled siRNA loaded DOPC liposomes (original siRNA concentration: 100 ng / μl), as second stage particles, were mixed with 1st stage large pore “LP” oxidized silicon particles (3.5 micron). Incubation was performed in 20 mM Tris pH 7.3 for 30 min at room temperature. The solution was spun down at 4,200 rpm for 1 min at room temperature. The supernatant was recovered and the fluorescence of the sample was measured by fluorimetry using 544 nm / 590 nm (excitation / emission) settings. The particle pellet comprising the 1st stage particles that had incorporated the fluorescent liposomes were resuspended in 100 μl of deionized water and fluorimetric readings were taken. The loading time dynamics...

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Abstract

Multistage delivery vehicles are disclosed which include a first stage particle and a second stage particle. The first stage particle is a micro or nanoparticle that contains the second stage particle. The second stage particle includes an active agent, such as a therapeutic agent or an imaging agent. The multistage delivery vehicle allows sequential overcoming or bypassing of biological barriers. The multistage delivery vehicle is administered as a part of a composition that includes a plurality of the vehicles. Methods of making the multistage delivery vehicles are also provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 60 / 821,750 filed Aug. 8, 2006, and U.S. Provisional Patent Application No. 60 / 914,348 filed Apr. 27, 2007, the disclosures of which are hereby incorporated herein by reference.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]The U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of DOD Grant No. W81XWH-04-2-0035 Project 16; NASA Grant No. SA23-06-017; and NIH Grant No. NC1 1R21CA1222864-01.BACKGROUND[0003]1. Technical Field[0004]The present inventions relate generally to the field of nanotechnology and, in particular, to compositions utilizing micro and / or nanoparticles for delivery active agents, such as therapeutic and imaging agents, and methods of making and methods of using s...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/02A61K47/30A61K39/395A61K9/127
CPCA61K9/51A61K31/165A61K31/704A61K31/7088A61K9/127A61K9/1271A61K9/50
Inventor FERRARI, MAUROTASCIOTTI, ENNIO
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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