Thermosensitive Poloxamer-graft-Carboxymethyl Pullulan: A Potential Injectable Hydrogel for Drug Delivery.

Marieta Constantin,Maria Bercea,Bogdan Cosman,Gheorghe Fundueanu,Gabriela-Liliana Ailiesei

doi:10.3390/polym13183025

Abstract

A thermosensitive copolymer composed of amphiphilic triblock copolymer, poloxamer 407, grafted on hydrophilic pullulan with pendant carboxymethyl groups (CMP) was prepared and characterized. The structure of the new copolymer was assessed by Fourier transform infrared (FT-IR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The content of the poloxamer in the grafted copolymer was 83.8% (w/w). The effect of the copolymer concentration on the gelation behavior was analyzed by the vertical method and rheological tests; the gel phase of the copolymer occurred at a lower concentration (11%, w/v) as compared with poloxamer (18%, w/v). The starting gelation time under the simulated physiological conditions (phosphate buffer with a pH of 7.4, at 37 °C) was sensitive on the rest temperature before the test, this being 990 s and 280 s after 24 h rest at 4 °C and 20 °C, respectively. The rheological tests evidenced a high elasticity and excellent ability of the copolymer to recover the initial structure after the removal of the applied force or external stimuli. Moreover, the hydrogel has proved a sustained release of amoxicillin (taken as a model drug) over 168 h. Taken together, the results clearly indicate that this copolymer can be used as an injectable hydrogel.

Highlights

Injectable hydrogels are attracting supports for drug delivery and tissue engineering applications due to their physical properties and minimally invasive delivery and adapting shape in real time [1,2]
The reaction occurred with the formation of an amide bond (Scheme 1) in the amino groups of functionalized poloxamer and carboxylic groups present on the thepullulan presence of The
Poloxamer-graft-carboxymethyl pullulan (Plx-g-CMP) copolymer was successfully synthesized by the coupling reaction between carboxymethyl groups of pullulan and amine groups introduced on poloxamer

Summary

Introduction

Injectable hydrogels are attracting supports for drug delivery and tissue engineering applications due to their physical ( manipulated) properties and minimally invasive delivery and adapting shape in real time [1,2]. The hydrogel precursor loaded with drugs and/or target cells can be injected at the wound site where it presents in situ sol–gel transition due to physical or chemical stimuli. Injectable hydrogels have a microstructure similar to the extracellular matrix (ECM) and allow good physical integration into the defect, possibly avoiding an open surgical procedure and facilitating the use of minimally invasive approaches to the delivery of materials and cells [2]. Injectable hydrogels can be prepared by physical or chemical crosslinking of polymers, the mechanical properties of the latter ones being considerably improved [3,4]. Other studies demonstrated that doses up to 8.75 mL of 22% Pluronic

Methods

Results

Conclusion