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Updated: May 9, 2026

Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by π-π Stacking Interactions
Published on: October 10, 2016
Physicochemical characterization, solubilization, and stabilization of 9-nitrocamptothecin using pluronic block
Sohodeb C Saha1, Deval Patel, Shahidur Rahman
1Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, 11201.
Abstract:
Solid-state properties and physicochemical characteristics of 9-nitrocamptothecin (9NC) were investigated with a view of molecular and bulk level understanding of its poor aqueous solubility and hydrolytic instability that prevent efficient drug delivery and pharmacological activity. 9NC bulk drug substance was found to be a nonhygroscopic, yellowish crystalline solid with long rectangular prism-shaped particle morphology and a sharp melting point at 264°C. Hydrolysis of 9NC-lactone occurs above pH 4, whereas complete conversion of lactone to carboxylate was recorded above pH 8. At saturated conditions, appreciable concentrations of 9NC-lactone were detected at pH as high as 11. 9NC undergoes oxidation in the presence of dimethyl sulfoxide with formation of 9NC-N-oxide. The total solubility of lactone and carboxylate forms of 9NC in deionized water was found to be less than 5 μg/mL, whereas the solubility of 9NC-lactone in aqueous acidic media was determined to be approximately 2.5 μg/mL. Incorporation of 10% pluronic copolymers P123, F127, and F68 in 10 mM HCl increased 9NC solubility by 13-fold, eightfold, and fivefold, respectively. The thermodynamic stability of drug-loaded pluronic micelles was evaluated under isothermal variable volume conditions and found F127, among all poloxamers, to offer the best hydrolytic protection efficacy for 9NC.
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