Chitosan-gadopentetic acid complex nanoparticles for gadolinium neutron-capture therapy of cancer : Preparation by novel emulsion-droplet coalescence technique and characterization

• Published in: Pharmaceutical research 1999-12, Vol.16 (12), p.1830-1835
• Main Authors: TOKUMITSU, H, ICHIKAWA, H, FUKUMORI, Y
• Format: Article
• Language: English
• Subjects: Acids; Animals; Aqueous solutions; Biological and medical sciences; Chemistry, Pharmaceutical; Chitin - administration & dosage; Chitin - analogs & derivatives; Chitin - chemistry; Chitin - pharmacokinetics; Chitosan; Contrast Media - administration & dosage; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Emulsions; Gadolinium DTPA - administration & dosage; Gadolinium DTPA - chemistry; Gadolinium DTPA - pharmacokinetics; General pharmacology; Injections; Magnetic resonance imaging; Male; Medical sciences; Melanoma; Melanoma, Experimental - radiotherapy; Mice; Mice, Inbred C57BL; Microspheres; Nanoparticles; Neoplasms - radiotherapy; Neutron Capture Therapy; Neutrons; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin cancer; Solutions; Viscosity
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/a:1018995124527

The gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared for gadolinium neutron-capture therapy (Gd-NCT) and characterized and evaluated as a device for intratumoral (i.t.) injection. Gd-nanoCPs were prepared by a novel emulsion-droplet coalescence technique. The effects of the deacetylation degree of chitosan and Gd-DTPA concentration in chitosan medium on the particle size and the gadolinium content in Gd-nanoCPs were examined. In vitro Gd-DTPA release from Gd-nanoCPs was evaluated using an isotonic phosphate-buffered saline solution (PBS, pH 7.4) and human plasma. In vivo Gd-DTPA retention in the tumor after i.t. injection of Gd-nanoCPs was estimated on mice bearing s.c. B16F10 melanoma. Gd-nanoCPs with the highest Gd content, which were obtained using 100% deacetylated chitosan in 15% Gd-DTPA aqueous solution, were 452 nm in diameter and 45% in Gd-DTPA content. A lower deacetylation degree of chitosan led to an increase in particle size and a decrease in Gd-DTPA content in Gd-nanoCPs. As Gd-DTPA concentration in the chitosan solution increased, Gd-DTPA content in Gd-nanoCPs increased but the particle size did not vary. Gd-DTPA loaded to Gd-nanoCPs was hardly released over 7 days in PBS (1.8%) despite the high water solubility of Gd-DTPA. In contrast, 91% of Gd-DTPA was released in plasma over 24 hours. When Gd-nanoCPs were i.t. injected, 92% of Gd-DTPA injected effectually without outflow was held in the tumor tissue for 24 hours, which was different from the case of gadopentetate solution injection (only 1.2%). Gd-nanoCPs highly incorporating Gd-DTPA were successfully prepared by the emulsion-droplet coalescence technique. Their releasing properties and their ability for long-term retention of Gd-DTPA in the tumor indicated that Gd-nanoCPs might be useful as an i.t. injectable device for Gd-NCT.