Dataset Information

A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix.

ABSTRACT: We have developed a "self-healing" polyglycerol sebacate-polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA)/?-Cyclodextrin (?CD) hydrogel which could be sheared into a liquid during injection and has the potential to quickly "heal" itself back into gel post-injection. This hydrogel was shown to be biocompatible and biodegradable and therefore appropriate for use in vivo. Furthermore, the storage and loss moduli of the hydrogels could be tuned (by varying the concentration of ?CD) between a fraction of a kPa to a few 100 kPa, a range that coincides with the moduli of cells and human soft tissues. This property would allow for this hydrogel to be used in vivo with maximal mechanical compatibility with human soft tissues. In vitro experiments showed that the hydrogel demonstrated a linear mass erosion profile and a biphasic drug (doxorubicin) release profile: Phase I was primarily driven by diffusion and Phase II was driven by hydrogel erosion. The diffusion mechanism was modeled with the First Order equation and the erosion mechanism with the Hopfenberg equation. This established fitting model could be used to predict releases with other drugs and estimate the composition of the hydrogel required to achieve a desired release rate.

SUBMITTER: Ye H

PROVIDER: S-EPMC6432133 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix.

Ye Hongye H Owh Cally C Jiang Shan S Ng Cavin Zhen Quan CZQ Wirawan Daniel D Loh Xian Jun XJ

Polymers 20160407 4

We have developed a "self-healing" polyglycerol sebacate-polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA)/α-Cyclodextrin (αCD) hydrogel which could be sheared into a liquid during injection and has the potential to quickly "heal" itself back into gel post-injection. This hydrogel was shown to be biocompatible and biodegradable and therefore appropriate for use <i>in vivo</i>. Furthermore, the storage and loss moduli of the hydrogels could be tuned (by varying the concentration of αCD) ...[more]

PMID: 30979218

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Project description:PurposeThe brain, protected by the cranium externally and the blood-brain barrier (BBB) internally, poses challenges in chemotherapy of aggressive brain tumors. Maximal tumor resection followed by radiation and chemotherapy is the standard treatment protocol; however, a substantial number of patients suffer from recurrence. Systemic circulation of drugs causes myelodysplasia and other side effects. To address these caveats, we report facile synthesis of a polyester-based supramolecular hydrogel as a brain biocompatible implant for in situ delivery of hydrophobic drugs.MethodsPolycaprolactone-diol (PCL) was linked to polyethyleneglycol-diacid (PEG) via an ester bond. In silico modeling indicated micelle-based aggregation of PCL-PEG co-polymer to form a supramolecular hydrogel. Brain biocompatibility was checked in Sprague Dawley rat brain cortex with MRI, motor function test, and histology. Model hydrophobic drugs carmustine and curcumin entrapment propelled glioma cells into apoptosis-based death evaluated by in vitro cytotoxicity assays and Western blot. In vivo post-surgical xenograft glioma model was developed in NOD-SCID mice and evaluated for efficacy to restrict aggressive regrowth of tumors.Results20% (w/v) PCL-PEG forms a soft hydrogel that can cover the uneven and large surface area of a tumor resection cavity and maintain brain density. The PCL-PEG hydrogel was biocompatible, and well-tolerated upon implantation in rat brain cortex, for a study period of 12 weeks. We report for the first time the combination of carmustine and curcumin entrapped as model hydrophobic drugs, increasing their bioavailability and yielding synergistic apoptotic effect on glioma cells. Further in vivo study indicated PCL-PEG hydrogel with a dual cargo of carmustine and curcumin restricted aggressive regrowth post-resection significantly compared with control and animals with intravenous drug treatment.ConclusionPCL-PEG soft gel-based implant is malleable compared with rigid wafers used as implants, thus providing larger surface area contact. This stable, biocompatible, supramolecular gel without external crosslinking can find wide applications by interchanging formulation of various hydrophobic drugs to ensure and increase site-specific delivery, avoiding systemic circulation.

Dataset Information

A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix.

Publications

A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix.

Similar Datasets

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