Inclusion complexes of noscapine in β-cyclodextrin offer better solubility and improved pharmacokinetics View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-02

AUTHORS

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

ABSTRACT

PURPOSE: 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 beta-cyclodextrin (beta-CD) and evaluated its physico-chemical characteristics. METHOD AND RESULTS: Our phase-solubility analysis shows a 1:1-complexation (Kc approximately 0.454 mM(-1)) of NOS with beta-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, 1H nuclear magnetic resonance spectroscopy, rotating frame Overhauser enhancement spectroscopy and by molecular modeling methods. Based upon theoretical calculations in gas phase, we propose O-CH2-O- in orientation of NOS in the beta-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 beta-CD inclusion complex state as compared to free NOS. Furthermore, the complex retains the anticancer attributes of NOS. CONCLUSION: Our studies propose for the first time a stable NOS-beta-CD inclusion complex as an effective approach to enhance the solubility and bioavailability of NOS for anticancer therapy. More... »

PAGES

537

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-009-1060-3

DOI

http://dx.doi.org/10.1007/s00280-009-1060-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014041999

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19597818


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49 schema:description PURPOSE: 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 beta-cyclodextrin (beta-CD) and evaluated its physico-chemical characteristics. METHOD AND RESULTS: Our phase-solubility analysis shows a 1:1-complexation (Kc approximately 0.454 mM(-1)) of NOS with beta-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, 1H nuclear magnetic resonance spectroscopy, rotating frame Overhauser enhancement spectroscopy and by molecular modeling methods. Based upon theoretical calculations in gas phase, we propose O-CH2-O- in orientation of NOS in the beta-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 beta-CD inclusion complex state as compared to free NOS. Furthermore, the complex retains the anticancer attributes of NOS. CONCLUSION: Our studies propose for the first time a stable NOS-beta-CD inclusion complex as an effective approach to enhance the solubility and bioavailability of NOS for anticancer therapy.
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