Drug Delivery via Hydrogels

Title: Self-assembling peptide–polysaccharide hybrid hydrogel as a potential carrier for drug delivery

Authors: Renliang Huang, Wei Qi, Libin Feng, Rongxin Su and Zhimin He

Journal: Soft Matter

Affiliation: State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University

Hydrogels are big networks of hydrophilic polymers.  These materials have many applications in drug delivery, tissue engineering, and a multitude of other biological applications.  In this work the authors create a hybrid hydrogel made of Fmoc-diphenylalanine (Fmoc-FF) peptide and konjac glucomannan (KGM), characterize this hydrogel, and study its ability to uptake and release drugs.

The researchers compare their new hybrid hydrogel with a hydrogel only consisting of Fmoc-FF peptide.  Just using visual cues, they determined that the hybrid hydrogel took longer to gel than the Fmoc-FF peptide hydrogel.  They also compared the stability of the two hydrogels by incubating them at 37 °C in pH 7.4 phosphate buffer solutions.  After two days the Fmoc-FF peptide hydrogel had completely destabilized.  Over the same time period the hybrid hydrogel remained stable.

The authors also characterized the hydrogels using rheology (the study of the flow of matter).  By observing the storage shear modulus and the loss shear modulus, the researchers were able to determine when the hydrogel had formed.  As they had observed visually, the Fmoc-FF peptide hydrogel formed faster than the hybrid hydrogel.   Additionally, the storage modulus for the hybrid hydrogel was found to be almost twice that of the Fmoc-FF peptide hydrogel indicating that the hybrid is more resilient mechanically.

To study drug uptake and release, the authors dissolved Fmoc-FF peptide with docetaxel, a chemotherapy agent.  These mixtures were then added to either water of a solution of KGM.  After aging for three days hydrogels impregnated with docetaxel were formed.  The researchers tuned a number of variables (KGM concentration, KGM molecular weight, aging time, and enzyme concentration in the medium) in order to study how the release of docetaxel could be controlled.  Release was slowed by increasing the concentration of KGM. Lower KGM molecular weights also led to slower release.  Shorter aging times led to faster release.  KGM is degraded by β-glycosidases, such as β-mannanase, so the authors investigated how the introduction of β-mannanase changed release time.  They found that β-mannanase could increase release by a large amount.  As β-glycosidases are largely concentrated in the colon, a KGM containing hydrogel is a good candidate for a drug carrier to the colon.  As a whole these experiments demonstrate the ability to tune the rate of drug release from hydrogels.

The authors conducted numerous other studies including some using SEM and TEM technology to investigate the morphology of the hydrogels.  This morphology can be used to explain some of the drug uptake and release results.

This paper introduces a new hydrogel that displays good properties for targeted drug delivery.  The methods used can be applied to design new hybrid hydrogels for a variety of applications.

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