Optimized fungal chitosan-based pegasparaginase immobilization for intravenous delivery to enhance treatment of acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is a crippling childhood cancer where usually a rare white blood cell runs amok, multiplying uncontrollably. Pegasparaginase, a vital weapon in the ALL arsenal, starves leukaemic cells by depleting asparagine, their lifeline. However, current treatments are plagued by issues like debilitating hypersensitivity, fleeting enzyme stability, and inadequate delivery methods. This review explores groundbreaking solution, the immobilization of pegasparaginase using fungal chitosan for direct intravenous administration. Cutting-edge computational modeling to optimize the enzyme–nanoparticle interaction ensures potent and long-lasting activity. IoT and IoMT integration with smart sensor would enable improved efficiency, decision making, and remote monitoring, while AI and ML can be utilized for drug discovery processes, optimizing drug design for therapeutic applications and forming nanomedicine-based treatment outcomes, respectively. Key parameters like enzyme loading, cross-linking density, and nanoparticle size were meticulously adjusted for peak therapeutic performance. The encapsulation process shields pegasparaginase from the harsh realities of the body, enabling controlled release and sustained enzyme activity. This transformed enzyme boasts improved pharmacokinetics, a longer lifespan and reduced hypersensitivity reactions overcoming the crippling limitations of existing therapies. This approach is particularly aligned with the needs of paediatric ALL patients, who are the majority and highly susceptible to side effects of treatment. Chitosan-based fungal nanoparticles offer a superior, controlled, and biocompatible delivery system, maximizing therapeutic potential of pegasparaginase, while minimizing immunogenic risks. To sum up, this study presents a novel and potent strategy for pegasparaginase immobilization, combining computational brilliance with experimental innovation to conquer the most pressing challenges in ALL treatment. These findings strongly suggest the potential of delivery systems to curb adverse reactions and amplify enzyme efficacy, making them a prime candidate for clinical applications. Future research should focus on scaling up production and conducting clinical trials to validate these findings and explore broader applications for enzyme-based therapies in other diseases. This review underscores the immense potential of integrating nanotechnology and permissible biocompatible materials to revolutionize therapeutic approaches in oncology.

Graphical Abstract