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

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.

• Authors: Matthew McKenzie, David Betts, Amy Suh, Kathryn Bui, Rui Tang, Kexian Liang, Samuel Achilefu, Glen S Kwon, Hyunah Cho
• Journal: Pharmaceutical research (Pharm Res) Vol. 33 Issue 9 Pg. 2298-306 (09 2016) ISSN: 1573-904X [Electronic] United States
• PMID: 27283829 (Publication Type: Journal Article)

Chemical References

• Drug Carriers
• Hydrogels
• Polyesters
• Polymers
• poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide)
• Polyethylene Glycols
• Paclitaxel
• Sirolimus

Topics

• Animals
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Female
• Hydrogels (chemistry)
• Injections, Intraperitoneal (methods)
• Mice
• Mice, Nude
• Ovarian Neoplasms (diet therapy)
• Paclitaxel (administration & dosage, chemistry)
• Peritoneal Neoplasms (drug therapy)
• Polyesters (administration & dosage, chemistry)
• Polyethylene Glycols (administration & dosage, chemistry)
• Polymers (chemistry)
• Sirolimus (administration & dosage, chemistry)
• Surgery, Computer-Assisted (methods)