# Thermoresponsive Graft Copolymers of N‑Isopropylacrylamide and Hyperbranched Polyglycerol as Thermally Induced Drug Delivery and Release Nanoformulation Systems for Curcumin with High Colloidal Stability and Enhanced Anticancer Effect

## TL;DR

This paper introduces a new type of temperature-sensitive polymer that can deliver curcumin, a natural anticancer compound, with improved stability and effectiveness against colon cancer cells.

## Contribution

The novel contribution is the development of thermoresponsive graft copolymers combining N-isopropylacrylamide and hyperbranched polyglycerol for efficient curcumin delivery.

## Key findings

- The graft copolymers enable efficient curcumin encapsulation and sustained release triggered by temperature changes.
- The nanoformulations significantly enhance curcumin's internalization and anticancer effect in colon cancer cells.
- The copolymers show excellent colloidal stability and no cytotoxicity in human cells.

## Abstract

The poor solubility,
stability issues, and restricted
bioavailability
of numerous drugs and potential pharmaceutical compounds highlight
the critical need for the development of polymeric nanoparticles as
effective drug delivery systems. Ideal polymers for such applications
must be biocompatible, provide controlled drug loading and release,
and maintain the high colloidal stability of the nanoformulation.
In this study, LCST-type thermoresponsive poly­(N-isopropylacrylamide)-g-(hyperbranched polyglycerol) (PNiPAAm-g-HbPG) graft copolymers, composed of two biocompatible components,
were synthesized by grafting amino-monofunctional HbPG, prepared by
multibranching anionic ring-opening polymerization, onto PNiPAAm chains
containing succinimide active ester groups. In both aqueous solutions
and phosphate-buffered saline, these graft copolymers undergo reversible
aggregation and disaggregation in response to temperature changes,
with linear increase of the critical solution temperature (CST) as
a function of grafting density. The architecture of the copolymers
enables efficient encapsulation of curcumin, a natural anticancer
agent, by a simple mixing process at elevated temperatures, and the
hydrophilic HbPG side chains provide excellent colloidal stability
for the polymer–drug nanoformulations. Sustained release of
curcumin from the PNiPAAm-g-HbPG aggregates was found,
which depends on the grafting density, and the release rate can be
externally triggered by decreasing the temperature. The potential
biocompatibility of the PNiPAAm-g-HbPG graft copolymers
was demonstrated in vitro, with no evidence of cytotoxicity
or hemolytic activity against human cells. The nanoformulations of
curcumin with these new graft copolymers enhanced its internalization
into HT-29 human colorectal adenocarcinoma cells and significantly
improved its cytostatic effect against colon cancer cells. These properties
of the novel PNiPAAm-g-HbPG graft copolymers make
them superior candidates for advanced drug encapsulation and delivery
systems.