In vivo controlled release of fenretinide from long-acting release depots for chemoprevention of oral squamous cell carcinoma recurrence

Autor: Daren Wang, Susan R. Mallery, Kari Nieto, Ping Pei, Steven P. Schwendeman
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Drug
Oncology
Male
medicine.medical_specialty
Fenretinide
media_common.quotation_subject
Pharmaceutical Science
Mice
Nude
02 engineering and technology
Pharmacology
Chemoprevention
Article
Excipients
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Polylactic Acid-Polyglycolic Acid Copolymer
In vivo
Internal medicine
Cell Line
Tumor
medicine
Animals
Anticarcinogenic Agents
Humans
Dissolution testing
Lactic Acid
media_common
Drug Implants
Drug Carriers
Cancer
021001 nanoscience & nanotechnology
medicine.disease
Controlled release
Xenograft Model Antitumor Assays
In vitro
PLGA
Drug Liberation
chemistry
Solubility
030220 oncology & carcinogenesis
Delayed-Action Preparations
Carcinoma
Squamous Cell
Mouth Neoplasms
Neoplasm Recurrence
Local
0210 nano-technology
Polyglycolic Acid
Popis: Local, long-acting release fenretinide (4HPR) millicylindrical implants were prepared and evaluated for their release kinetics in vivo and their ability to suppress oral cancer tumor explant growth. Poly(lactic-co-glycolic acid)(PLGA) implants were prepared as a function of drug loading and the presence of various excipients (pore-formers, solubilizers, crystallization inhibitors) to enhance release of the insoluble 4HPR. Release kinetics and bioerosion of PLGA were monitored both in vitro in a PBS/Tween 80 buffer and in vivo by recovery of the drug remaining at the injection site. 4HPR was released from PLGA implants much slower in vivo than in the drug solubilizing media in vitro, with a 3-week lag phase and continuous release of >2 months, but showed some release enhancement by addition of solubilizers. Water-soluble PVA/sucrose implants for release of 4HPR served to determine if drug dissolution provided suitable controlled release without the PLGA, and this formulation showed continuous drug release over 6 weeks in vivo. Placement of PLGA-4HPR implants adjacent to oral cancer tumor murine xenografts showed inhibition of tumor growth relative to sham implants, indicating the potential for the local 4HPR delivery approach to be useful for oral cancer chemoprevention.
Databáze: OpenAIRE
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