TECHNICAL FIELD

The subject matter of this invention relates to hydrogel compositions and, more particularly, to hydrogel compositions comprising block copolymers (BCPs) capable of self-assembly into nanoparticles for the delivery and controlled release of therapeutic cargos.

BACKGROUND

Block copolymers (BCPs) comprise two or more covalently-linked homopolymer subunits, each homopolymer subunit made up of polymerized mononers. Block copolymers made up of two homopolymer subunits are referred to as diblock copolymers, those with three homopolymer subunits are referred to as triblock copolymers, etc. In any BCP, the junction of homopolymer units may, in some cases, include a junction block, a non-repeating subunit.

BCPs may be formed using any number of techniques, including, for example, atom transfer free radical polymerization (ATRP), reversible addition fragmentation chain transfer (RAFT), and ring-opening metathesis polymerization (ROMP), as will be appreciated by one skilled in the art.

Although BCPs have been used in many contexts, of more recent interest is their use in the encapsulation and delivery of other molecules, including drugs. When used in such methods, an amphiphilic BCP is made to form a micelle, with the molecule to be delivered contained therein.

Polymer-based micelles provide several advantages over other nano-carriers, such as liposomes. Among these advantages are their small size (10-100 nm), a reasonably low polydisperity index, and the ability to combine a hydrophobic core and a hydrophilic shell. The hydrophobic core facilitates the loading of hydrophobic cargo, including hydrophobic drugs, while the hydrophilic shell provides improved stability in aqueous environments.

Body tissues and cellular components have varying pH values. Blood and normal extracellular matrix, for example, have a pH of about 7.4, while the pH of a tumor extracellular environment is about 6.5, attributable to a lower oxygen supply in the intercellular environment. The pH in endosomes and lysosomes is even lower (5.0-5.5).

Some polymer-based micelles have been constructed to target tumor tissues and tumor cells based on this difference in pH. However, these have suffered from various deficiencies, including poor target specificity and lethargic drug release at the target site. In addition, it has been discovered that such micelles must be within a relatively narrow size range to be effective in most applications. Particles larger than about 100 nm, for example, have been found not to efficiently penetrate the extensive vasculature of most tumors. At the same time, micelles less than about 10 nm in size are below the renal threshold and are rapidly flushed from tumor sites and excreted.

SUMMARY

Aspects of the disclosure provide hydrogels comprising BCPs and methods for their manufacture and use.

A first aspect provides a hydrogel composition comprising: a first ABA triblock copolymer having negatively charged A blocks; and a second ABA triblock copolymer having positively charged A blocks.

A second aspect provides a hydrogel composition comprising: an AB diblock copolymer having a negatively charged A block; and an ABA triblock copolymer having positively charged A blocks.

A third aspect provides a micellar particle comprising: a hydrogel composition comprising: a first ABA triblock copolymer having negatively charged A blocks; and a second ABA triblock copolymer having positively charged A blocks; and at least one agent for delivery within the hydrogel composition.

A fourth aspect provides a micellar particle comprising: a hydrogel composition comprising: a first ABA triblock copolymer having negatively charged A blocks; and a second ABA triblock copolymer having positively charged A blocks; and at least one agent for delivery within the hydrogel composition.

A fifth aspect provides a method of treating, in an individual in need of such treatment, a disease or disorder amenable to treatment with a therapeutic agent, the method comprising: administering to the individual a hydrogel composition selected from a group consisting of: (a) a hydrogel composition comprising: a first ABA triblock copolymer having negatively charged A blocks; a second ABA triblock copolymer having positively charged A blocks; and at least one agent for delivery within the hydrogel composition; and (b) a hydrogel composition comprising: an AB diblock copolymer having a negatively charged A block; and a third ABA triblock copolymer having positively charged A block; and at least one agent for delivery within the hydrogel composition.

