Sustained-release PLGA-based nanoformulated solutions for drug delivery and targeting in paediatric solid and haematological malignancies

Abstract

Pediatric brain tumors continue to be one of the leading causes of death among children due to cancer because of the inadequacies of existing treatments, which include poor tumor selectivity, poor permeability across the blood-brain barrier, resistance to treatment, and high levels of side effects on developing tissue. Recent advances in nanotechnology-based treatments have been identified as potential strategies to counter these problems, with poly(lactic-co-glycolic acid) (PLGA) nanoparticles gaining a lot of traction due to their biodegradability, biocompatibility, and clinical translatability. PLGA nanocarriers present a versatile system that allows for improved treatment efficacy through precise drug release, pharmacokinetic advantages, and tumor-targeted delivery without causing systemic toxicity. The ability of PLGA carriers to incorporate different types of drugs, such as chemotherapy, nucleic acids, and combination therapies, presents an opportunity to circumvent multidrug resistance and increase the efficacy of treatments in pediatric cancers. Surface modification with targeting molecules, peptides, antibodies, and stimuli-sensitive agents also allows for receptor-mediated drug delivery and utilization of specific features of the tumor microenvironment for targeted drug release. This is especially relevant to pediatric brain tumors, which pose additional obstacles due to biological barriers and heterogeneous nature. Several recent studies have shown that PLGA nanoparticles can be used to optimize biodistribution, enable tissue penetration, influence the tumor microenvironment, and increase antitumor efficacy while decreasing side effects. In this review, the potential application of PLGA nanoparticles in the treatment of childhood brain tumors is discussed based on existing knowledge of the physicochemical properties of PLGA and approaches for its use in targeted drug delivery. Recent developments in the field of PLGA nanoparticle-based therapy and its clinical applications in children are highlighted, especially concerning the improvement of therapeutic localization and precision treatment of pediatric brain tumors.