Bridging solubility, stability, and translation: advances in carbon nanotube-based drug delivery systems.

Abstract

Background: Poor aqueous solubility and physicochemical instability remain major barriers in pharmaceutical development, limiting the bioavailability, therapeutic efficacy, and translational success of numerous drug candidates. Carbon nanotubes (CNTs), owing to their high surface area, tunable surface chemistry, and unique π-conjugated structure, have emerged as multifunctional nanocarriers capable of addressing these persistent formulation challenges.

Methodology: This review critically analyzes recent advances (2020-2026) in CNT-based drug delivery systems with emphasis on solubility enhancement, stability modulation, surface functionalization strategies, protein corona dynamics, dual functionalization approaches, nano-encapsulation technologies, and translational barriers. Comparative evaluation of covalent and non-covalent modification techniques, co-delivery platforms, dispersion strategies, and regulatory considerations is presented to assess their impact on clinical applicability.

Results: Functionalized CNTs demonstrate significantly improved aqueous dispersibility, enhanced drug-loading efficiency via π-π stacking and electrostatic interactions, and protection of labile therapeutics against enzymatic and chemical degradation. Polymer conjugation, ligand-directed targeting, and dual functionalization approaches enable controlled and stimuli-responsive release, particularly in tumour-specific microenvironments. Emerging insights into protein corona kinetics reveal their decisive role in biodistribution, immune recognition, and targeting efficiency. Recent innovations in co-delivery systems, lipid coating, and green synthesis further enhance formulation stability and bioavailability. However, challenges related to reproducible functionalization, aggregation control, scalable manufacturing, and regulatory standardisation continue to limit clinical translation.

Conclusion: CNT-based drug delivery systems offer a versatile and structurally adaptable platform to bridge solubility, stability, and translational gaps in modern pharmaceutics. While substantial progress has been achieved in enhancing dispersion behaviour, drug protection, and targeting precision, successful clinical implementation will depend on predictive biocompatibility engineering, standardised characterisation protocols, and scalable safe-by-design manufacturing strategies.