Pharmaceutical Research

, Volume 33, Issue 9, pp 2298–2306 | Cite as

Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer

  • Matthew McKenzie
  • David Betts
  • Amy Suh
  • Kathryn Bui
  • Rui Tang
  • Kexian Liang
  • Samuel Achilefu
  • Glen S. Kwon
  • Hyunah Cho
Research Paper

Abstract

Purpose

The purpose of this study is to investigate a sol–gel transition property and content release profiles for thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly-(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogels carrying paclitaxel, rapamycin, and LS301, and to present a proof-of-concept that PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, called TheranoGel, exhibit excellent theranostic activity in peritoneal ES-2-luc ovarian cancer xenograft mice.

Methods

Thermosensitive PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, individually or in combination, were prepared via a lyophilization method, characterized with content release kinetics, and assessed with theranostic activity in ES-2-luc xenograft mice.

Results

A thermosensitive PLGA-b-PEG-b-PLGA sol–gel system was able to entrain 3 poorly water-soluble payloads, paclitaxel, rapamycin, and LS301 (TheranoGel). TheranoGel made a sol-to-gel transition at 37°C and slowly released 3 drugs at a simultaneous release rate in response to the physical dissociation of hydrogels in vitro. TheranoGel enabled loco-regional delivery of multi-drugs by forming a gel-depot in the peritoneal cavity of ES-2-luc xenograft mice. An intraperitoneal (IP) administration of TheranoGel resulted in excellent therapeutic and diagnostic activities, leading to the improved peritoneal surgery in ES-2-luc xenograft mice.

Conclusions

TheranoGel prepared via a facile lyophiliation method enabled successful IP delivery of multi-drugs and exhibited excellent theranostic activity in vivo.

KEY WORDS

hydrogels intraperitoneal ovarian cancer theranostics thermosensitive 

ABBREVIATIONS

17-AAG

17-allylamino-17-demethoxygeldanamycin

BLI

Bioluminescence intensity

BLU

Bioluminescence

FLU

Fluorescence

IP

Intraperitoneal

IV

Intravenous

LS301

Cysteine-glycine-arginine-aspartic acid-serine-proline-cystein-lysine-cypate

Luc

Luciferase

mTOR

Mammalian target of rapamycin

NIR

Near infrared

PEG-b-PLA

Poly-(ethylene glycol)-block-(D,L-lactide)

PLGA-b-PEG-b-PLGA

(D,L-lactide-co-glycolide)-block-poly-(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide)

TheranoGel

PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301

TheranoMic

PEG-b-PLA micelles carrying paclitaxel, rapamycin, and LS301

Supplementary material

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ESM 1

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High resolution image (TIF 32 kb)
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ESM 2(AVI 229 kb)
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ESM 3(AVI 107 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Matthew McKenzie
    • 1
  • David Betts
    • 1
  • Amy Suh
    • 1
  • Kathryn Bui
    • 1
  • Rui Tang
    • 2
  • Kexian Liang
    • 2
  • Samuel Achilefu
    • 2
  • Glen S. Kwon
    • 3
    • 4
  • Hyunah Cho
    • 1
  1. 1.Department of Pharmaceutical and Administrative SciencesSt. Louis College of PharmacySt. LouisUSA
  2. 2.Department of RadiologyWashington University School of MedicineSt. LouisUSA
  3. 3.Pharmaceutical Sciences Division, School of PharmacyUniversity of WisconsinMadisonUSA
  4. 4.Faculty of PharmacyKing Abdulaziz UniversityJeddahSaudi Arabia

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