Details

Autor(en) / Beteiligte

• Madan, Jitender
• Dhiman, Neerupma
• Parmar, Vinod K
• Sardana, Satish
• Bharatam, Prasad V
• Aneja, Ritu
• Chandra, Ramesh
• Katyal, Anju

Titel

Inclusion complexes of noscapine in [beta]-cyclodextrin offer better solubility and improved pharmacokinetics

Ist Teil von

• Cancer chemotherapy and pharmacology, 2010-02, Vol.65 (3), p.537

Ort / Verlag

Heidelberg: Springer Nature B.V

Erscheinungsjahr

2010

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Noscapine (NOS) is a unique class of tubulin-binding anticancer agents. Their potential usefulness as anticancer drugs is however limited by the poor bioavailability, thus necessitating administration of a higher dose regime in the range of 300-600 mg/kg for tumor growth inhibition. To augment bioavailability, we prepared an inclusion complex of NOS in β-cyclodextrin (β-CD) and evaluated its physico-chemical characteristics. Our phase-solubility analysis shows a 1:1-complexation (K ^sub c^ ~0.454 mM^sup -1^) of NOS with β-CD that offers better dissolution properties. We confirmed complex formation in solid state by differential scanning calorimetry, powder X-ray diffractometry, Fourier-transform infrared spectroscopy, ^sup 1^H nuclear magnetic resonance spectroscopy, rotating frame Overhauser enhancement spectroscopy and by molecular modeling methods. Based upon theoretical calculations in gas phase, we propose O-CH^sub 2^-O- in orientation of NOS in the β-CD cavity. The thermal behavior data also provides complementary evidences of complex formation. The pharmacokinetic studies showed a 1.87-fold increase in bioavailability of NOS upon complexation in the β-CD inclusion complex state as compared to free NOS. Furthermore, the complex retains the anticancer attributes of NOS. Our studies propose for the first time a stable NOS-β-CD inclusion complex as an effective approach to enhance the solubility and bioavailability of NOS for anticancer therapy.[PUBLICATION ABSTRACT]