Acute and Repeated Dose Toxicity Studies of Different β-Cyclodextrin-Based Nanosponge Formulations
Section snippets
INTRODUCTION
Cyclodextrin-based nanosponges (NS) are spherical, regular shape, cross-linked nanoparticles. NS emerge with promising results in different fields such as medicine as drug carrier, drug solubiliser, controlled-release matrix system; agriculture as longevity enhancing agent for fruits and flowers; water purification as adsorbing agent, fire engineering as smoke adsorbent and flame retardant and so on.1 NS are condensed, complexed and/or polymerised β-cyclodextrin (β-CD) with different
Materials
β-Cyclodextrin was gifted from Roquette Italia SpA (Cassano Spinola, Italy). CDI, PMDA, HMDI and potassium hydroxide were obtained from Sigma-Aldrich (Munich, Germany). Dichloromethane, dimethyl formamide (DMF), acetone, dimethyl sulfoxide (DMSO), triethyl amine (TEA) and ethanol were purchased from Sigma-Aldrich (Munich, Germany). All other chemicals and reagents were of analytical grade.
Preparation of Cross-Linked NS
The cross-linked NS were prepared in 1:8 molar ratio of β-CD and CDI or HMDI or PMDA (Table 1) by the
Particle Size
The particle sizes of NS formulations were between 400 and 550 nm in CM and 50 and 200 nm in NM (Table 2) with low polydispersity indices (data not shown). It suggests that particle size of NS depends on process of grinding as well as the preparation method. The particle sizes of NS were 450–550 nm by trituration and 40–60 nm by vibrational rod milling.4
Acute Toxicity Study
After single oral administration of NS samples at 300 and 2000 mg/kg dose levels, animals in all treated groups did not show any lethal effects or
DISCUSSION
Toxicological evaluation is an important step to determine safety of drugs and excipients; it also helps for selection of safe dose for their use in humans and animals.
It is worth of note that the fate of the parent cyclodextrins in the gastrointestinal tract differs based on the resistance to hydrolysis and enzymatic degradation. The β-CDs are practically resistant to stomach acid or salivary and pancreatic amylases and they are extensively hydrolyzed in the colon.11 A human study with healthy
CONCLUSIONS
All NS after oral administration to rats were found safe at selected doses in acute and repeated dose toxicity study. Thus, the study provides first systematic report on toxicity data of these hyper cross-linked cyclodextrin polymers after oral administration, showing a good biocompatibility with a potential negligible degradation during the gastrointestinal transit. Despite that, further investigations are needed to evaluate the fate of NS in the GI tract. On the basis of the results, β-CD NS
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