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



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.



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.



TheranoGel prepared via a facile lyophiliation method enabled successful IP delivery of multi-drugs and exhibited excellent theranostic activity in vivo.
Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA.
Matthew
M
McKenzie
Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA.
David
D
Betts
Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA.
Amy
A
Suh
Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA.
Kathryn
K
Bui
Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Rui
R
Tang
Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Kexian
K
Liang
Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Samuel
S
Achilefu
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, 53705, USA.|Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Glen S
GS
Kwon
Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, Missouri, 63110, USA. Hyunah.Cho@stlcop.edu.
Hyunah
H
Cho
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D020100:Hydrogels / Q000737:chemistry*; D007274:Injections, Intraperitoneal / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000178:diet therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D020123:Sirolimus / Q000008:administration & dosage / Q000737:chemistry; D025321:Surgery, Computer-Assisted / Q000379:methods
D004337:Drug Carriers; D020100:Hydrogels; D011091:Polyesters; D011108:Polymers; C000595637:poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D017239:Paclitaxel; D020123:Sirolimus
hydrogels; intraperitoneal; ovarian cancer; theranostics; thermosensitive