Claire Fuller

The bioavailability of small-molecule drugs remains a critical challenge in pharmaceutical development, significantly impacting therapeutic efficacy and commercial viability. This review synthesizes recent advances in understanding and overcoming bioavailability limitations, focusing on key physicochemical and biological factors influencing drug absorption and distribution. We examine cutting-edge strategies for enhancing bioavailability, including innovative formulation approaches, rational structural modifications, and the application of artificial intelligence in drug design. The integration of nanotechnology, 3D printing, and stimuli-responsive delivery systems are highlighted as promising avenues for improving drug delivery. We discuss the importance of a holistic, multidisciplinary approach to bioavailability optimization, emphasizing early-stage consideration of ADME properties and the need for patient-centric design. This review also explores emerging technologies such as CRISPR-Cas9-mediated personalization and microbiome modulation for tailored bioavailability enhancement. Finally, we outline future research directions, including advanced predictive modeling, overcoming biological barriers, and addressing the challenges of emerging therapeutic modalities. By elucidating the complex interplay of factors affecting bioavailability, this review aims to guide future efforts in developing more effective and accessible small-molecule therapeutics.

Gliomas are the most common primary malignant tumours of the central nervous system (CNS), which are highly aggressive, with increasing morbidity and mortality rates year after year, posing a serious threat to the quality and expected survival time of patients. The treatment of gliomas is a major challenge in the field of neuro-oncology, especially high-grade gliomas such as glioblastomas (GBMs). Despite considerable progress in recent years in the study of the molecular and cellular mechanisms of GBMs, their prognosis remains bleak. Tumour-associated macrophages (TAMs) account for up to 50% of GBMs, and they are a highly heterogeneous cell population whose role cannot be ignored. Here, we focus on reviewing the contribution of classically activated M1-phenotype TAMs and alternatively activated M2-phenotype TAMs to GBMs, and exploring the research progress in reprogramming M1 TAMs into M2 TAMs.