N-Phthaloylchitosan-g-mPEG design for all- trans retinoic acid-loaded polymeric micelles

• Published in: European journal of pharmaceutical sciences Vol. 30; no. 5; pp. 424 - 431
• Main Authors: Opanasopit, Praneet, Ngawhirunpat, Tanasait, Rojanarata, Theerasak, Choochottiros, Chantiga, Chirachanchai, Suwabun
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.04.2007; Elsevier
• Subjects: All- trans retinoic acid; Antineoplastic Agents - chemistry; Antineoplastic Agents - radiation effects; Biological and medical sciences; Chemistry, Pharmaceutical; Chitosan - analogs & derivatives; Chitosan - chemistry; Controlled release; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Stability; Ethanol - chemistry; General pharmacology; Medical sciences; Micelles; Microscopy, Electron, Transmission; N-Phthaloylchitosan; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Photolysis; Polyethylene Glycols - chemistry; Polymeric micelles; Solubility; Solvents - chemistry; Surface Properties; Technology, Pharmaceutical; Tretinoin - chemistry; Tretinoin - radiation effects; Ultraviolet Rays; All- trans retinoic acid; Controlled release; Polymeric micelles; N-Phthaloylchitosan; Antineoplastic agent; Pharmaceutical technology; Controlled release form; Control release polymer; Retinoid; Micelle; Design; All-trans retinoic acid; Dosage form; Tretinoin
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2007.01.002

The amphiphilic grafted copolymer N-phthaloylchitosan-grafted poly(ethylene glycol) methyl ether (PLC-g-mPEG) was synthesized using chitosan with four different degrees of deacetylations (DD) (80, 85, 90 and 95%). All- trans retinoic acid (ATRA) was incorporated into PLC-g-mPEG by dialysis method in an attempt to optimize carriers for ATRA delivery. Morphological investigation by transmission electron microscopy (TEM) showed that the particles had round and uniform shapes. The particle sizes of ATRA incorporated into micelles were about 80–160 nm depending on the initial drug-loaded and %DD of chitosan. Physicochemical properties of ATRA-loaded polymeric micelles were also investigated. It was found that %DD of chitosan, which corresponded to the N-phthaloyl groups in the inner core of the micelles, was a key factor in controlling the incorporation efficiency, stability of the drug-loaded micelles and drug release behavior. As the %DD increased, the incorporation efficiency and ATRA-loaded micelles stability increased. The sustained release profiles were also obtained at high %DD (90 and 95%). When compared to the unprotected ATRA, ATRA loaded in PLC-g-mPEG micelles was efficiently protected from photodegradation. This result suggested that loading of ATRA in micelles improved the chemical stability of ATRA.