Influence of the Method of Preparation on the Characteristics and Performance of Cholesterol-based Polymeric Nanoparticles for Redox-triggered Release of Doxorubicin in Tumor Cells

In this study the influence of the method of preparation on the characteristics and bio-responsiveness of doxorubicin-loaded redox-sensitive nanoparticles (DOX-SS-NPs), formed by a biocompatible cholesterol-based amphiphilic block copolymer (PC5MA-SS-PEO) was investigated. Two commonly used preparation techniques: 1) cosolvent removal and 2) an O/W emulsion method were compared and the in vitro and in vivo performance of promising formulations was assessed. Besides particle size distribution and drug loading, the response of the nanoparticles to reducing environments and subsequent release kinetics and cytotoxicity were also affected by the method of preparation. The investigation and understanding of this extensive influence, led to a DOX-SS-NPs formulation with significant in vivo efficacy and an improved safety profile when evaluated against free doxorubicin (DOX-HCl) and the commercial pegylated liposomal form (Doxil®). Our findings highlight the importance of formulation optimization and support the use of systematic approaches like Quality by Design to the development of bio-responsive nanomedicines for cancer treatment.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research