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

Autor: Samuel Achilefu, Matthew McKenzie, Kathryn Bui, Hyunah Cho, Glen S. Kwon, David Betts, Kexian Liang, Rui Tang, Amy Suh
Rok vydání: 2016
Předmět:
medicine.medical_specialty
Paclitaxel
Polymers
Polyesters
Pharmaceutical Science
Mice
Nude
02 engineering and technology
macromolecular substances
Article
Polyethylene Glycols
03 medical and health sciences
chemistry.chemical_compound
Peritoneal cavity
Mice
0302 clinical medicine
Drug Delivery Systems
In vivo
medicine
Animals
Pharmacology (medical)
Peritoneal Neoplasms
Pharmacology
Ovarian Neoplasms
Sirolimus
Drug Carriers
Organic Chemistry
technology
industry
and agriculture
Hydrogels
021001 nanoscience & nanotechnology
medicine.disease
Surgery
medicine.anatomical_structure
chemistry
Surgery
Computer-Assisted
030220 oncology & carcinogenesis
Drug delivery
Self-healing hydrogels
Cancer research
Molecular Medicine
Female
0210 nano-technology
Ovarian cancer
Drug carrier
Ethylene glycol
Injections
Intraperitoneal
Biotechnology
Zdroj: Pharm Res
ISSN: 1573-904X
Popis: 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.
Databáze: OpenAIRE
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