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Biodegradable liquogel and ph sensitive nanocarriers

a liquogel and nanocarrier technology, applied in the field of temperature responsive liquogel and ph sensitive nanocarriers, can solve the problems of biological non-degradability, deleterious effects in patients, and systemic therapy does not necessarily provide therapeutic tissue level of a drug

Inactive Publication Date: 2013-08-22
NORTH CAROLINA CENTRAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a delivery system that uses hyperbranched polyglycerols (HPG) to form a liquogel and a pH-sensitive nanocarrier for carrying drugs or therapeutic agents. This system can be used to administrate drugs or agents locally. Overall, the invention provides a new way to deliver molecules to specific locations in the body.

Problems solved by technology

For treatment of certain diseases and conditions, systemic therapy does not necessarily provide therapeutic tissue levels of a drug.
It may also result in deleterious effects in the patient.
However, all of these representative thermally smart polymers include hydrophilic materials that are biologically non-degradable on any useful timescale.
Although the copolymers discussed above represent feasible options for developing in situ gelling biomaterials-indeed a prototype PNIPAAm-based delivery system has been used in animal models with compromised ventricular architecture of the heart [9], limitations exist with respect to extending the utility of one delivery system to more than one application.
No ideal drug delivery system has been designed to date.
Local delivery of drugs embedded in a hyperbranched polyglycerol (HPG) based nanocarrier has the potential to reduce the need for surgical and other procedures that are time consuming for the patient and can result in complications to the patient.

Method used

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  • Biodegradable liquogel and ph sensitive nanocarriers
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  • Biodegradable liquogel and ph sensitive nanocarriers

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0117]HPG (Mn,MALDI=1096 g mol−1, Mw / Mn=1.13) was prepared according to the literature by controlled anionic polymerization of glycidol [21], The average number of terminal hydroxyl groups per HPG molecule was approximately 29 as determined by the relative integrals from the inverse gated 13C NMR spectra. (FIG. 21) Glycidyl methacrylate (GMA), Acrylic acid (AAc), and N-isopropylacrylamide (NIPAAm) were purchased from Sigma-Aldrich (St. Louis, Mo.). AAc was purified immediately prior to use by passage through a basic alumina column. NIPAAm was recrystallized from hexane and vacuum dried. Benzoyl peroxide (BPO), stannous 2-ethylhexanoate [(Sn(Oct)2],(3S)-cis-3,6 Dimethyl-1,4-dioxane,-2,5 dione (98%) (L-lactide), 4-(N,N-diethylamino)pyridine (DMAP), anhydrous dimethyl sulfoxide (DMSO), anhydrous 1,4-dioxane, methyl sulfoxide-d6 (99.9% atom D), anhydrous methanol, tetrahydrofuran (THF), and phosphate-buffered saline (PBS) were purchased from Fisher Scientific (Pittsburgh, Pa.). All poly...

example 2

[0134]The thermoresponsive nature of a liquogel according to the invention in 16.5 wt % phosphate buffered saline (PBS) solution was investigated to determine the lower critical solubility temperature (LCST) at which gelling begins to occur. The solution that is clear at 10° C. progresses to cloudy at 24° C. to a solid gel at 35° C. These results are shown in Table 2 and FIG. 18.

TABLE 2Qualitative observation of the liquogel gelation temperatureTemperature (° C.)Visual Appearance0Clear24Cloudy28Solid firming30More liquid + solid35Gels

[0135]The LCST was also investigated by measurement of the liquogel solution optical absorption as a function of temperature using UV / Vis spectroscopy and differential scanning calorimetry differential scanning calorimetry (DSC). Scanning the liquogel solution at 500 nm over the temperature range of 0° C. to 43.3° C. (see FIG. 19), the temperature at which the optical absorption rapidly transitions (the LCST) occurs around 35° C. This was also confirmed...

example 4

[0138]The cytotoxic effects of a pH triggered delivery system of fulvestrant, camptothecin or nanocarrier on MCF-7 cells is shown in FIGS. 16 and 17. Comparison of cytotoxic effects by Fulvestrant, Camptothecin and Nanocarrier.

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Abstract

A delivery system using materials that form a liquogel or nanocarrier are described. The delivery system comprises hyperbranched polyglycerols (HPGs). The delivery system can include a drug or therapeutic agent and this system can be used to administer the drug or therapeutic agent locally. The delivery system provides for controlled release of the drug or therapeutic agent.

Description

[0001]This invention was supported in part by funds from the U.S. Government NIH / ORWH BIRCWH 5 K12 HD043446-04, NIH 5-G11-HD041831-05 EARDA and DMR-0959679. The U.S. government may therefore have certain rights in the invention.FIELD OF THE INVENTION[0002]The present invention relates to a temperature responsive liquogel and pH sensitive nanocarriers.BACKGROUND OF THE INVENTION[0003]For treatment of certain diseases and conditions, systemic therapy does not necessarily provide therapeutic tissue levels of a drug. It may also result in deleterious effects in the patient. As such there is a need for a local delivery system that can be used to deliver a drug or therapeutic agent locally to a specific site.[0004]A number of synthetic hydrogels with a lower critical solution temperature (LCST) below body temperature have been touted as promising injectable drug delivery systems [1-7]. Hydrogels are often used in biological applications thus they are often biomaterials. Hydrogels swell in...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/34
CPCA61K9/0024A61K9/06A61K31/4745A61K31/565A61K47/34A61K47/48107C08L101/005A61K47/48192C08G83/006C08L101/16A61K47/551A61K47/59
Inventor TAYLOR, DARLENE K.OCHIENG, MELONY A.
Owner NORTH CAROLINA CENTRAL UNIVERSITY
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