Bifunctional-modified hydrogels

a technology of hydrogels and bifunctional molecules, applied in the field of hydrogels, can solve the problems of limited efficacy of current materials used in the construction of biomedical devices, multi-functional structures, and dressings that do not address, and achieve the effects of preventing swelling of the wound bed, facilitating gas exchange, and maintaining humidity and oxygen levels

Inactive Publication Date: 2006-05-11
KAO WEIYUAN +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014] The novel hydrogel constructs described herein are not physical blends, which are common in the formulation of current biomedical hydrogels; hence, the chemical and physical properties of the subject hydrogels are homogenous and can be tailored to suit a particular clinical end-point requirement. Furthermore, the hydrogel constructs are mechanically stable because the components are covalently bonded. In addition, the hydrophilicity and flexibility of the porous hydrogel accommodate the absorption of wound exudate and assist the final removal of the material from the wound site (if necessary or desired). The nature of gelatin and the porosity of the construct further facilitate the exchange of gases and allow healing. Most importantly, the presence of hPEG-conjugated bioactive compounds and the loading of other pharmaceutical compounds within the matrix allows for the temporally- and spatially-controlled delivery of bioactive signals to modulate and complement the dynamics of the host healing process.
[0015] The present invention offers several key commercial advantages over existing products. For example, despite the extensive investigation in the development of novel wound dressing materials, very few materials are used clinically due to the multiple requirements necessary for a functional wound dressing. Ideal functional wound dressings must be nontoxic, biocompatible, permeable to moisture and gases to absorb wound exudate and toxins, as well as to maintain humidity and oxygen levels. The dressings should be porous to prevent swelling of the wound bed and to prevent accumulation of fluid between the wound site and the material. They should be flexible and durable. They should be biocompatible and minimize local inflammation and infection. They should promote neovascularization, re-epithelialization, and normal healing. The novel multi-functional hydrogels described herein can be made to address all of the above requirements for a clinically viable wound dressing material.

Problems solved by technology

The efficacy of current materials used to construct biomedical devices is limited by a lack of multi-functional structures to complement the inherent dynamics of these biological systems.
However, these dressings do not address, for example, the exudation which occurs from a wound.
However, these types of dressing have no therapeutic effect.
While such types of dressings provide effective barriers to physical disturbance of the wound site, scarring is still extensive.
Despite the extensive investigation of novel wound dressing materials, very few materials are in current clinical use.

Method used

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Examples

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example 1

Synthesis and Characterization of Heterobifunctional PEGs

[0149] All reagents were purchased from Sigma-Aldrich (St. Louis, Mo.) unless stated otherwise. A summary of the chemical reactions and structure of critical intermediates and final products is presented in FIG. 1.

[0150] To synthesize α-methyl-ω-acrylate PEGs (M-PEG), monomethoxy PEGs (2 kDa or 5 kDa, purchased from Fluka, a division of Sigma-Aldrich) were dissolved in dry tetrahydrofuran (THF) solution followed by the addition of triethylamine (TEA, 2 eq.) and acryloyl chloride (AC, 4 eq.)(14) at room temperature under Ar for 10 min, filtered, dried by rotary evaporation, re-dissolved in CH2Cl2, and precipitated in cold hexane. The final product was filtered, dried, and stored in vacuo at room temperature.

[0151] To synthesize α-cyanoethyl-ω-acrylate-PEGs (CN-PEG), PEG-diols (2 kDa or 5 kDa) (1 eq.) were dissolved in dry CH2Cl2 solution followed by the addition of fine sodium metal (2 eq.) stirred for 12 hr at room temperat...

example 2

Drug Release Kinetics

[0172] This Example explores the swelling and drug release kinetics of various gelatin-based hydrogels. The hydrogels were cross-linked by various means, and contained various modifications of the gelatin backbone. The effect of pH on the drug release kinetics of these gels was also investigated.

[0173] As noted above, cross-linking gelatin produces a hydrogel of high molecular weight and reduces or prevents gelatin dissolution. The cross-linking agents used in this Example were: 0.1%, 0.01%, and 0.001% (v / v) glutaraldehyde aqueous solutions, and self-cross-linking via liquid nitrogen immersion followed by baking. The backbone modifications to the gelatin were the addition of polyethylene glycol (PEG) or ethylenediaminetetraacetic dianhydride (EDTAD) or both. PEG has low immunogenicity and cytotoxicity. EDTAD has low toxicity and the lysyl residues of gelatin can be modified with EDTAD in a relatively fast reaction following facile procedures. See Hwang & Damod...

example 3

In Vivo Modulation of Host Response Using Gels Grafted with Fibronectin-Derived Biomimetic Oligopeptides

[0184] The host inflammatory reaction is a normal response to injury and the presence of foreign objects. The magnitude and duration of the inflammatory process have a direct impact on biomaterial biostability and biocompatability. Thus, this Example investigates the performance of gels fabricated according to the present invention that include fibronectin-derived biomimetic oligopeptides. Fibronectin in known to adsorb on a variety of biomaterials and play an important role in the host-foreign body reaction. The RGD (SEQ. ID. NO: 1) and PHSRN (SEQ. ID. NO: 2) amino acid sequences are particularly interesting because these sequences are present on adjacent loops of two connecting FIII modules and bind synergistically to a host of integrins.

[0185] Oligopeptides were designed based on the primary and tertiary structure of human plasma fibronectin to study the structure-functional ...

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Abstract

Disclosed are hydrogels wherein a polymer matrix is modified to contain a bifunctional poly(alkylene glycol) molecule covalently bonded to the polymer matrix. The hydrogels can be cross-linked using, for example, glutaraldehyde. The hydrogels may also be crosslinked via an interpenetrating network of a photopolymerizable acrylates. The hydrogels may also be modified to have pharmacologically-active agents covalently bonded to the poly(alkylene glycol) molecules or entrained within the hydrogel. Living cells may also be entrained within the hydrogels.

Description

PRIORITY [0001] Priority is hereby claimed to provisional application Ser. No. 60 / 285,782, filed 23 Apr. 2001, the entire contents of which is incorporated herein.FEDERAL FUNDING [0002] This invention was made with United States government support awarded by the following agencies: NIH HL63686. The United States has certain rights in this invention.FIELD OF THE INVENTION [0003] The invention is directed to hydrogels modified using bifunctional reagents, use of the hydrogels to deliver drugs or other biologically-active agents to a mammal in need thereof, compositions containing the hydrogels described herein, and devices, such as wound dressings, diapers, catamenial devices, etc., incorporating the hydrogels. INCORPORATION BY REFERENCE [0004] All of the reference listed in the “References” section are incorporated herein. BACKGROUND [0005] Biological systems, such as healing and embryonic development, operate under spatially- and temporally-controlled orchestration. A myriad of sign...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/48A61K9/06A61K47/32A61K47/38A61K47/42A61L15/22A61L15/32A61L15/60A61L27/00C08G81/00C08L101/14C12N5/02
CPCA61K47/48215A61K47/48784A61L15/225A61L15/32A61L15/325A61L15/60C08G81/00C08L101/14C08L89/06A61K47/60A61K47/6903Y10S530/815Y10S530/817
Inventor KAO, WEIYUANLI, JINGLOK, DAVIDGUNDLOORI, RATHNA
Owner KAO WEIYUAN
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