Development of water-soluble nanoformulations of novel pyrazolone derivatives and the evaluation of their antibacterial and antioxidant activities

Abstract

Poor aqueous solubility and stability hinder the clinical translation of pyrazolone-based derivatives despite their various biological activities. This study aimed to address these issues by developing water-soluble nanoformulations of two specific pyrazolone derivatives, Compounds I and II, selected based on their promising structural features and previous biological activity data. PLGA/poloxamer-based nanoformulations were prepared and optimized for size, PDI, zeta potential (ZP), and entrapment efficiency (EE). The optimized formulations demonstrated sizes of 166.6 ± 7.12 nm and 192.5 ± 1.08 nm, PDI of 0.129 ± 0.042 and 0.132 ± 0.025, ZP of − 14.14 ± 2.90 mV and − 10.77 ± 1.515 mV, and %EE of 84.20 ± 0.930 and 81.5 ± 2.051, respectively. A sustained drug release was observed over 48 h, with cumulative releases of approximately 37% and 53%, for both formulations, and characterized by a complex drug release behavior. The formulations exhibited significant antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus (SA), with greater than 90% cell death for SA and greater than 80% for MRSA, observed using the flow cytometer. Also, enhanced antioxidant activity was observed using DPPH, FRAP, and NO methods, showing better radical scavenging than standard gallic acid and bare compounds. The hemolysis assay confirmed the biocompatibility of the developed formulation, with a hemolysis percentage of less than 5%. This study highlights the successful development of water-soluble nanoformulations with significant antibacterial and antioxidant activities, emphasizing the impact of solubility enhancement on biological efficacy and suggesting potential pharmaceutical applications for these agents.