Matthew McKenzie1, David Betts1, Amy Suh1, Kathryn Bui1, Rui Tang2, Kexian Liang2, Samuel Achilefu2, Glen S Kwon3,4, Hyunah Cho5. 1. Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA. 2. Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA. 3. Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, 53705, USA. 4. Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. 5. Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA. Hyunah.Cho@stlcop.edu.
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.
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.
Authors: Yang Liu; Adam Q Bauer; Walter J Akers; Gail Sudlow; Kexian Liang; Duanwen Shen; Mikhail Y Berezin; Joseph P Culver; Samuel Achilefu Journal: Surgery Date: 2011-05 Impact factor: 3.982
Authors: Monica M Mita; Alain C Mita; Quincy S Chu; Eric K Rowinsky; Gerald J Fetterly; Michelle Goldston; Amita Patnaik; Lesley Mathews; Alejandro D Ricart; Theresa Mays; Heather Knowles; Victor M Rivera; Jeff Kreisberg; Camille L Bedrosian; Anthony W Tolcher Journal: J Clin Oncol Date: 2008-01-20 Impact factor: 44.544
Authors: Anne O'Donnell; Sandrine Faivre; Howard A Burris; Daniel Rea; Vassiliki Papadimitrakopoulou; Nicholas Shand; Heidi A Lane; Katharine Hazell; Ulrike Zoellner; John M Kovarik; Cathryn Brock; Suzanne Jones; Eric Raymond; Ian Judson Journal: J Clin Oncol Date: 2008-03-10 Impact factor: 44.544