Quercetin-Based Advanced Delivery Systems – From Multimodal Nano-theranostics to Microneedles: a Recent Update on Their Preclinical Studies

Maya Beena,1,2 Anjaneyulu Udduttula,2,* Arunkumar Palaniappan3,* 1School of Bioscience and Technology (SBST), Vellore Institute of Technology, Vellore, Tamil Nadu, India; 2Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology, Vellore, Tamil Nadu, India; 3Department of Biotechnology, Birla Institute of Technology & Science, Pilani (BITS Pilani) - Dubai Campus, Dubai, United Arab Emirates*These authors contributed equally to this workCorrespondence: Arunkumar Palaniappan, Email [email protected] Anjaneyulu Udduttula, Email [email protected]: Quercetin is a naturally derived flavonoid that has received growing attention for its wide range of pharmacological activities such as strong anticancer, antimicrobial, anti-inflammatory, and antioxidant effects. Its multiple functions and natural bioactivity make it an appealing therapeutic candidate. However, the clinical use of quercetin is still limited by issues like poor water solubility, low bioavailability, fast metabolism, and difficulties in achieving targeted delivery. Recent research has aimed to overcome these challenges through innovative formulation strategies like nanoencapsulation, polymeric carriers, 3D printing, microneedle scaffolds and surface modification. These approaches improve stability, boost bioavailability, and allow for targeted therapeutic effects. Traditional theranostic systems that use nanoparticles, quantum dots, or linked biomolecules have enhanced precision medicine by merging diagnostic imaging methods, such as MRI, PET, and fluorescence, with treatment options like targeted drug delivery and photothermal therapy. Yet, these systems face issues related to biocompatibility, cost, biodegradability, and targeting precision. Platforms based on quercetin are emerging as a promising alternative to tackle these problems. Despite their potential, this area is largely uncharted, and, to our knowledge, no thorough review has focused on quercetin’s role in multifunctional theranostic systems. This review offers a systematic look at the design strategies, biomedical uses, and potential for quercetin-based theranostics. We discuss key challenges, such as achieving controlled/stimuli-responsive delivery, validation in higher animal studies, scale-up and to emphasize future directions for evolving quercetin-based platforms as next-generation nano-theranostics.Keywords: quercetin, theranostics, microneedle, 3D bioprinted, pharmaceuticals, multifunctional