Abstract: The present disclosure relates to a polymeric system for release of an active agent, comprising a first polymeric phase containing the active agent, the first polymeric phase forming discrete regions of a set size range and being dispersed within a second polymeric phase comprising a cross-linked polymer-phenol conjugate for release of the active agent therein. The present disclosure further provides an injectable hydrogel comprising the disclosed polymeric system, a carrier for delivering a biologically active substance or a drug comprising the injectable hydrogel, and a method for producing the disclosed polymeric system.

Abstract: There is provided methods for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid including a method for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid. There is also provided a method for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid without the addition of an exogenous peroxide or peroxidase or without the addition of an exogenous peroxide. Hydrogels produced by such methods and methods of using the hydrogels are also described herein.

Abstract: There are provided methods for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid, formed from a reaction using peroxide and peroxidase. Hydrogels produced by such methods and methods of using the hydrogels are also provided.

Abstract: There is provided a method of forming a hydrogel, the method comprising: providing a mixture of a polymer comprising a cross-linkable pendant phenolic group, peroxidase, H2O2, fibrinogen, and thrombin, at concentration sufficient to enzymatically cross-link the polymer and to cleave the fibrinogen to yield fibrin; and allowing the mixture to form a hydrogel. There is also provided a hydrogel comprising a cross-linked network of a polymer interpenetrated by fibrin fibers, the polymer cross-linked by oxidative coupling between phenolic groups pendant on the polymer.

Abstract: There is presently provided a suspension of immiscible particles in a solution, wherein the particles comprise an agglomeration of a bioactive agent; and a plurality of conjugates of a hyaluronic acid and a flavonoid wherein the particles are on average from about 15 nm to about 300 nm in diameter and wherein the bioactive agent is releasably retained in the particles by the flavonoid. There is also provided a therapeutic formulation comprising such a suspension and methods for using the suspension and therapeutic formulation, including for delivery of a bioactive agent to a cell and for treating a disease, including cancer.

Abstract: A polymer fiber is formed by hydrodynamic spinning. Fluids are forced to flow through a conduit to form a laminar flow comprising three or more layers of generally coaxial fluid flows, at respective flow rates selected to define a cross-section of a tubular middle layer of the fluid flows. The middle layer comprises a cross-linkable polymer precursor. Another layer of the fluid flows comprise a cross-linking agent. The polymer precursor, cross-linking agent and fluids are selected to prevent substantial diffusion of the polymer precursor away from the middle layer, and to allow a portion of the cross-linking agent to diffuse from the another layer into the middle layer to facilitate cross-linking of the polymer precursor in the middle layer to form a tubular polymer layer in a polymer fiber. The polymer layer thus has a cross-section generally corresponding to the cross-section of the middle layer.

Abstract: There is presently provided a suspension of immiscible particles in a solution, wherein the particles comprise an agglomeration of a bioactive agent, for example an anti-cancer agent; and a plurality of conjugates of a hyaluronic acid and a flavonoid, for example a catechin-based flavonoid, wherein the particles are on average from about 15 nm to about 300 nm in diameter and wherein the bioactive agent is releasably retained in the particles by the flavonoid. The suspension is useful for the delivery of the bioactive agent to cells, including cancer cells. There are also provided a therapeutic formulation comprising the suspension, as well as methods for using the suspension and therapeutic formulation, including for delivery of a bioactive agent to a cell and for treating a disease, including cancer.

Abstract: In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (H2O2), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of H2O2 and concentration of HRP in the solution when the molarity of H2O2 is limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of H2O2 may be selected to affect the differentiation or growth rate of the cells in the hydrogel. Also, the hydrogel system may be used for sustained delivery of a therapeutic protein, for example in the treatment of liver cancer, fibrosis or hepatitis.

Abstract: There are provided methods for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid, formed from a reaction using peroxide and peroxidase. Hydrogels produced by such methods and methods of using the hydrogels are also provided.

Abstract: There are provided methods for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid, formed from a reaction using peroxide and peroxidase. Hydrogels produced by such methods and methods of using the hydrogels are also provided.

Abstract: There is provided a method of conjugating a polymer containing a free aldehyde group with a flavonoid in the presence of an acid catalyst, such that the polymer is conjugated to the C6 or C8 position of the flavonoid A ring. The resulting conjugates may be used to form delivery vehicles to deliver high doses of flavonoids, and may also be used as delivery vehicles to deliver an additional bioactive agent.

Abstract: A composite is disclosed. The composite comprises a first conjugate of a polymer and a first phenol-containing moiety, and a second conjugate of a gelatin or collagen and a second phenol-containing moiety, wherein the polymer is selected so that the first conjugate is less cell-adhesive than the second conjugate, at least one of the first and second conjugates is crosslinked to form a matrix, and the composite comprises discrete regions that are rich in one of said first and second conjugates. A method of forming such composite is also disclosed. The method comprises mixing precursors for the first and second conjugates in a solution for forming said composite, and dispersing a catalyst in the solution to catalyze crosslinking of at least one of the first and second conjugates to form the matrix. The composite may be used to grow cells.

Abstract: There is provided a conjugate of a delivery agent containing a chemical moiety and at least one flavonoid. The flavonoid exists in a monomeric form or dimeric form before conjugation and remains in the monomeric form or dimeric form after conjugation. Preferably, the conjugate comprises two flavonoids. The delivery agent is conjugated at the C6 and/or the C8 position of the A ring of the flavonoid. An anti-cancer agent delivery vehicle comprising an anti-cancer agent and the conjugate is also provided.

Abstract: There is provided a method of forming a hydrogel, the method comprising: providing a mixture of a polymer comprising a cross-linkable pendant phenolic group, peroxidase, H2O2, fibrinogen, and thrombin, at concentration sufficient to enzymatically cross-link the polymer and to cleave the fibrinogen to yield fibrin; and allowing the mixture to form a hydrogel. There is also provided a hydrogel comprising a cross-linked network of a polymer interpenetrated by fibrin fibers, the polymer cross-linked by oxidative coupling between phenolic groups pendant on the polymer.

Abstract: In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (H2O2), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of H2O2 and concentration of HRP in the solution when the molarity of H2O2 is limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of H2O2 may be selected to affect the differentiation or growth rate of the cells in the hydrogel.

Abstract: In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (H2O2), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of H2O2 and concentration of HRP in the solution when the molarity of H2O2 is limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of H2O2 may be selected to affect the differentiation or growth rate of the cells in the hydrogel. Also, the hydrogel system may be used for sustained delivery of a therapeutic protein, for example in the treatment of liver cancer, fibrosis or hepatitis.

Abstract: There is presently provided a suspension of immiscible particles in a solution, wherein the particles comprise an agglomeration of a bioactive agent; and a plurality of conjugates of a hyaluronic acid and a flavonoid wherein the particles are on average from about 15 nm to about 300 nm in diameter and wherein the bioactive agent is releasably retained in the particles by the flavonoid. There is also provided a therapeutic formulation comprising such a suspension and methods for using the suspension and therapeutic formulation, including for delivery of a bioactive agent to a cell and for treating a disease, including cancer.

Abstract: There is provided methods for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid including a method for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid. There is also provided a method for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid without the addition of an exogenous peroxide or peroxidase or without the addition of an exogenous peroxide. Hydrogels produced by such methods and methods of using the hydrogels are also described herein.

Abstract: There is provided a method of conjugating a polymer containing a free aldehyde group with a flavonoid in the presence of an acid catalyst, such that the polymer is conjugated to the C6 or C8 position of the flavonoid A ring. The resulting conjugates may be used to form delivery vehicles to deliver high doses of flavonoids, and may also be used as delivery vehicles to deliver an additional bioactive agent.

Abstract: There is provided a method of conjugating a polymer containing a free aldehyde group with a flavonoid in the presence of an acid catalyst, such that the polymer is conjugated to the C6 or C8 position of the flavonoid A ring. The resulting conjugates may be used to form delivery vehicles to deliver high doses of flavonoids, and may also be used as delivery vehicles to deliver an additional bioactive agent.