Agency for Science, Technology and Research

Joo Eun Chung

Motoichi Kurisawa

Fan Lee

Jackie Yi-Ru Ying

Yi Yan Yang

Li Wang

Lang Zhuo

Min-Han Tan

Ki Hyun Bae

Pui Yik Peggy Chan

Shengyong Ng

Esther Lee

Yongvongsoontorn Nunnarpas

Susi Tan

Kun Liang

Keming Xu

Hirohisa Yano

Pui Yik Chan

Jackie Y Ying

Kurisawa Motoichi

Li Shan Wang

The present invention relates to micellar nanocomplexes and a method of forming the same. The micellar nanocomplex comprises a micelle and an agent encapsulated within said micelle, where the micelle comprises a polymer-flavonoid conjugate, wherein said polymer is bonded to the B ring of said flavonoid. The micellar nanocomplex may have useful applications as a drug-delivery system.

Micellar polymer-flavonoid conjugate nanocomplex

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.

Phase separated composite

Micellar nanocomplex

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.

Anti-cancer agent delivery vehicles capable of improved loading

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.

Methods for producing crosslinked flavonoid hydrogels

There is provided a delivery vehicle comprising an anti-cancer agent together with a conjugate of a delivery agent containing a free aldehyde and a flavonoid, having the delivery agent conjugated at the C6 and/or the C8 position of the A ring of the flavonoid. The resulting delivery vehicles may be used to deliver an anti-cancer agent to a cell.

Method of delivering an anti-cancer agent to a cell

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 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.

Particulate hyaluronic acid and flavonoid formulations for cellular delivery of bioactive agents

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.

Cell-adhesive, enzymatically crosslinked flavonoid hydrogels and methods for making same

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.

Particulate hyaluronic acid/flavonoid suspensions for cellular delivery of bioactive agents

In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (HO), 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 HOand concentration of HRP in the solution when the molarity of HOis 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 HOmay 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.

Formation of hydrogel in the presence of peroxidase and low concentration of hydrogen peroxide

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.

Aldehyde conjugated flavonoid preparations

In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (HO), 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 HOand concentration of HRP in the solution when the molarity of HOis 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 HOmay be selected to affect the differentiation or growth rate of the cells in the hydrogel.

Growing community of inventors

Singapore, Singapore

Joo Eun Chung