# Engineering Extended Release Profiles for Biologic Formulations via Chemical Cross-Linking of Poloxamer 407 Hydrogels

## TL;DR

This paper describes a method to improve the stability and drug release of P407 hydrogels by chemically cross-linking them, enabling long-term delivery of biologics.

## Contribution

Chemically cross-linked P407 hydrogels with tunable release profiles for biologics are developed using acrylate and thiol-based cross-linkers.

## Key findings

- Chemical cross-linking enhanced the mechanical strength and stability of P407 hydrogels.
- The hydrogels enabled extended in vitro release of biologics for up to 70 days.
- Biophysical tests confirmed that the hydrogels preserved the structure and function of encapsulated biologics.

## Abstract

Hydrogels,
networks of hydrophilic polymers known for
their water
retention capacity, biodegradability, and biocompatibility, are ideal
for the sustained and extended delivery of biologics. Because in
situ hydrogels can form at the administration site in response to
external stimuli, they can provide noninvasive and localized delivery
of biotherapeutics. In particular, poloxamer 407 (P407), an “A–B–A”
triblock copolymer, composed of hydrophilic poly­(ethylene oxide) (block
A) and hydrophobic poly­(propylene oxide) (block B), exhibits reversible
thermal property: liquid at room temperature and gelling at elevated
temperatures. This characteristic, combined with its low toxicity
and excellent chemical compatibility, makes P407 an attractive polymer
for drug delivery applications. However, its low mechanical strength
and weak gel stability have limited its broader use in therapeutic
applications. To address this challenge, chemically cross-linked P407
hydrogels were developed using acrylate-modified P407 and thiol-terminated
eight-arm polyethylene glycol with two different molecular weights
(MWs) via Michael-type addition. Chemical cross-linking enhanced the
mechanical strength of P407 hydrogels, enabling extended in vitro
release of bovine serum albumin (BSA), human plasma immunoglobulin
G antibody (IgG), and adalimumab for up to 70 days with tunable release
kinetics profile. Biophysical and functional characterization via
circular dichroism, size exclusion chromatography, capillary electrophoresis-sodium
dodecyl sulfate, and enzyme-linked immunosorbent assay indicated that
the hydrogels did not adversely affect the structural conformation,
stability, and in vitro potency of the encapsulated biologics. This
study highlights improved P407 hydrogel stability and tunable release
profiles by incorporating acrylate reactive cross-linkers with two
different MWs, providing insights for the application of sustained
and controlled release of biologic.