Abstract: There is growing evidence about the efficacy of natural compounds and peptides as central-acting anti-obesity drugs; on the other hand, their pharmacokinetic profile often hampers the clinical application. In this narrative review, the critical role of nanomedicine and peptide conjugation is reported as a promising strategy to overcome these limits. The focus areas were centrally acting drugs for obesity, providing context about pathways involved and past and currently approved medications, pointing out their limits. The last 10 years research was analyzed to collect the progress in central-acting anti-obesity drugs and the new potential strategies (nanomedicine and conjugation), with attention on natural compounds and peptides. Based on literature review, nanocarriers and conjugation strategies can offer targeted delivery of both natural molecules and peptides, enhancing their therapeutics, improving cellular uptake, and regulating metabolism and inflammatory pathways. The choice of the proper administration route, along with a delivery strategy significantly impacts the pharmacokinetics and therapeutic outcomes of compounds delivered through nanomedicines and encourages their translation ‘from bench to bedside.’
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