Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations

• Published in: Journal of pharmaceutical sciences Vol. 104; no. 5; p. 1856
• Main Authors: Shende, Pravin, Kulkarni, Yogesh A, Gaud, R S, Deshmukh, Kiran, Cavalli, Roberta, Trotta, Francesco, Caldera, Fabrizio
• Format: Journal Article
• Language: English
• Published: United States 01-05-2015
• Subjects: Animals; beta-Cyclodextrins - administration & dosage; beta-Cyclodextrins - chemistry; beta-Cyclodextrins - toxicity; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Female; Male; Nanospheres - administration & dosage; Nanospheres - chemistry; Nanospheres - toxicity; Rats; Rats, Wistar; Toxicity Tests, Acute - methods; repeated dose toxicity; OECD guidelines; protein delivery; acute toxicity; nanotechnology; pharmacokinetics; interfacial condensation method; complexation; cyclodextrin nanosponge; bulk condensation method; surface active
• ISSN: 1520-6017
• DOI: 10.1002/jps.24416

Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.