SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer
Journal Title: AAPS PharmSciTech - Year 2014, Vol 15, Issue 2
Abstract
SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether β-cyclodextrin (SBEβCD), hydroxypropyl β-cyclodextrin, randomly methylated β-cyclodextrin, and methyl β-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-βCD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBEβCD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an AP-type system. Aqueous solubility of SN-38 was enhanced by about 30–1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBEβCD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBEβCD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBEβCD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications.
Authors and Affiliations
Kiran Kumar Vangara, Hamed Ismail Ali, Dai Lu, Jingbo Louise Liu, Srikanth Kolluru, Srinath Palakurthi
Keywords
Related Articles
- EP ID EP682381
- DOI 10.1208/s12249-013-0068-5
- Views 80
- Downloads 0
Injectable Supramolecular Hydrogel from Insulin-Loaded Triblock PCL-PEG-PCL Copolymer and γ-Cyclodextrin with Sustained-Release Property
Supramolecular hydrogels formed by cyclodextrins and polymers have been widely investigated as a biocompatible, biodegradable and controllable drug delivery system. In this study, a supramolecular hydrogel based on biode...
The Improvement of the Dissolution Rate of Ziprasidone Free Base from Solid Oral Formulations
This work aims at increasing solubility and dissolution rate of ziprasidone free base—Biopharmaceutics Classifaction System (BCS) class II compound. The authors describe a practical approach to amorphization and...
Lyophilized Sustained Release Mucoadhesive Chitosan Sponges for Buccal Buspirone Hydrochloride Delivery: Formulation and In Vitro Evaluation
This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/fr...
Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics
Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes....
Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach
The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process...