Quality-by-design optimized albumin nanoparticles encapsulating Artemisia annua L. phytochemicals using artemisinin
Anuradha Mishra1, Saman Fatima2, Firdaus Qamar1
1Centre for Transgenic Plant Development, Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
Abstract:
Herbal therapeutics continue to play a pivotal role in drug discovery; however, their clinical translation is often limited by poor aqueous solubility, low bioavailability, rapid systemic clearance, and batch-to-batch variability. Artemisia annua L. represents these challenges due to the physicochemical instability and pharmacokinetic limitations of its principal bioactive, artemisinin (ART), along with associated phytochemicals. In this study, a robust nano-delivery system for A. annua whole-leaf extract (AAWLE) was developed using a Quality-by-Design (QbD)-guided approach. Human serum albumin nanoparticles (HSA-NPs) were fabricated following quantitative estimation of ART in AAWLE, which served as a marker for batch-to-batch consistency and reproducibility. A fractional factorial design (fFD) was applied for systematic screening of critical material attributes (CMAs) and critical process parameters (CPPs) influencing critical quality attributes (CQAs), including particle size (PS), polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE). Further optimization through a Box-Behnken-design (BBD) established a statistically validated design space. The optimized AAWLE-HSA-NPs exhibited a PS ˂100 nm, PDI of 0.23, and zeta potential of -22.11 mV, indicating good colloidal stability, along with high drug-loading capacity and particle yield of ∼95%. In vitro release studies demonstrated a biphasic release profile with an initial burst followed by sustained drug release. Under simulated gastrointestinal conditions, the AAWLE-HSA-NPs showed minimal size variation (91.27-99.80 nm) and sustained EE (>93%), confirming controlled drug retention within the physiological absorption window. Overall, this study demonstrates a QbD-guided nanotechnology approach for the development of reproducible AAWLE-HSA-NPs that exhibited acceptable stability, favorable physicochemical characteristics, and sustained in vitro release behavior.
