Formulation and evaluation of biodegradable nanoparticles for the oral delivery of fenretinide

• Published in: European journal of pharmaceutical sciences Vol. 76; pp. 1 - 9
• Main Authors: Graves, Richard A., Ledet, Grace A., Glotser, Elena Y., Mitchner, Demaurian M., Bostanian, Levon A., Mandal, Tarun K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.08.2015
• Subjects: Administration, Oral; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Biodegradable; Caco-2 Cells; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Carriers; Esters - chemistry; Fenretinide; Fenretinide - administration & dosage; Fenretinide - chemistry; Fenretinide - metabolism; Formulation; Humans; Intestinal Absorption; Intestinal Mucosa - metabolism; Kinetics; Lactic Acid - chemistry; Mass Spectrometry; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Permeability; Polyethylene Glycols - chemistry; Polyglactin 910 - chemistry; Polyglycolic Acid - chemistry; Polymers - chemistry; Solubility; Spectrophotometry, Ultraviolet; Technology, Pharmaceutical - methods; Fenretinide (Pubchem CID: 5288209); Nanoparticles; Fenretinide; Biodegradable; Formulation
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2015.04.024

[Display omitted] Fenretinide is an anticancer drug with low water solubility and poor bioavailability. The goal of this study was to develop biodegradable polymeric nanoparticles of fenretinide with the intent of increasing its apparent aqueous solubility and intestinal permeability. Three biodegradable polymers were investigated for this purpose: two different poly lactide-co-glycolide (PLGA) polymers, one acid terminated and one ester terminated, and one poly lactide-co-glycolide/polyethylene glycol (PLGA/PEG) diblock copolymer. Nanoparticles were obtained by using an emulsification solvent evaporation technique. The formulations were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and particle size analysis. Dissolution studies and Caco-2 cell permeation studies were also carried out for all formulations. Ultra high performance liquid chromatography coupled with mass spectrometry (UPLC/MS) and ultraviolet detection was used for the quantitative determination of fenretinide. Drug loading and the type of polymer affected the nanoparticles’ physical properties, drug release rate, and cell permeability. While the acid terminated PLGA nanoparticles performed the best in drug release, the ester terminated PLGA nanoparticles performed the best in the Caco-2 cell permeability assays. The PLGA/PEG copolymer nanoparticles performed better than the formulations with ester terminated PLGA in terms of drug release but had the poorest performance in terms of cell permeation. All three categories of formulations performed better than the drug alone in both drug release and cell permeation studies.