Development and Evaluation of Stable Long Circulating Decitabine-loaded Copolymeric Nanoparticles: Harnessing QbD Approach and Lyophilization Technique

Purpose Decitabine is an inhibitor of DNA methyltransferase used to treat various types of leukemias. However, it is highly unstable in nature thereby needing an innovative intervention to harness its benefits. Thus, the study aimed to develop a stable nano-formulation of decitabine with improved pharmacokinetic characteristics. Method In the present study, the Quality by Design approach was employed to systematically design and optimize decitabine-loaded nanoparticles. The nanoparticles were fabricated with emulsion solvent diffusion method and screened by 2 K-1 fractional factorial design followed by Box-Behnken design to obtain nanoparticles with desirable characteristics. The optimized uncoated formulation was surface-modified to obtain PEGylated nanoparticles. The developed nanoparticles were further lyophilized using a suitable lyophilization cycle to obtain highly stable decitabine-loaded nanoparticles. The developed nanoformulations were assessed with in vitro and in vivo evaluation. Result The lyophilized decitabine-loaded, uncoated and PEGylated nanoparticles exhibited a particle size of 194.5 nm and 177.9 nm and zeta potential of -32.9 mV and − 31.0 mV, respectively. Also, these exhibited a desirable encapsulation efficiency of 85.2% and 90.9%, respectively. The developed nanoformulations indicated a prolonged drug release over a period of 7 h. The in vivo study confirmed the improved pharmacokinetic parameters for drug-loaded nanoparticles in comparison to drug solution. Conclusion The drug-loaded lyophilized nanoparticles were successfully developed and showcased superior quality attributes in both in vitro and in vivo assessments. This study thereby underscores the possible application of this nano-therapeutic system for leukemia treatment with implications for the broader landscape of nanomedicine and precision technology.