The major impediment to the delivery of therapeutics to the brain is the presence of the blood-brain barrier (BBB). The BBB allows for the entrance of essential nutrients while excluding harmful substances, including most therapeutic agents; hence, brain disorders, especially tumours, are very difficult to treat. Chitosan is a well-researched polymer that offers advantageous biological and chemical properties, such as mucoadhesion and the ease of functionalisation. Chitosan-based nanocarriers (CsNCs) establish ionic interactions with the endothelial cells, facilitating the crossing of drugs through the BBB by adsorptive mediated transcytosis. This process is further enhanced by modifications of the structure of chitosan, owing to the presence of reactive amino and hydroxyl groups. Finally, by permanently binding ligands or molecules, such as antibodies or lipids, CsNCs have showed a boosted passage through the BBB, in both in vivo and in vitro studies which will be discussed in this review.

Clustered regularly interspaced short palindromic repeat (CRISPR) and the associated Cas endonuclease (Cas9) is a cutting-edge genome-editing technology that specifically targets DNA sequences by using short RNA molecules, helping the endonuclease Cas9 in the repairing of genes responsible for genetic diseases. However, the main issue regarding the application of this technique is the development of an efficient CRISPR/Cas9 delivery system. The consensus relies on the use of non-viral delivery systems represented by nanoparticles (NPs). Chitosan is a safe biopolymer widely used in the generation of NPs for several biomedical applications, especially gene delivery. Indeed, it shows several advantages in the context of gene delivery systems, for instance, the presence of positively charged amino groups on its backbone can establish electrostatic interactions with the negatively charged nucleic acid forming stable nanocomplexes. However, its main limitations include poor solubility in physiological pH and limited buffering ability, which can be overcome by functionalising its chemical structure. This review offers a critical analysis of the different approaches for the generation of chitosan-based CRISPR/Cas9 delivery systems and suggestions for future developments.

The use of RNA interference mechanism and small interfering RNA (siRNA) in cancer gene therapy is a very promising approach. However, the success of gene silencing is underpinned by the efficient delivery of intact siRNA into the targeted cell. Nowadays, chitosan is one of the most widely studied non-viral vectors for siRNA delivery, since it is a biodegradable, biocompatible and positively charged polymer able to bind to the negatively charged siRNA forming nanoparticles (NPs) that will act as siRNA delivery system. However, chitosan shows several limitations such as low transfection efficiency and low solubility at physiological pH. Therefore, a variety of chemical and non-chemical structural modifications of chitosan were investigated in the attempt to develop a chitosan derivative showing the features of an ideal siRNA carrier. In this review, the most recently proposed chemical modifications of chitosan are outlined. The type of modification, chemical structure, physicochemical properties, siRNA binding affinity and complexation efficiency of the modified chitosan are discussed. Moreover, the resulting NPs characteristics, cellular uptake, serum stability, cytotoxicity and gene transfection efficiency in vitro and/or in vivo are described and compared to the unmodified chitosan. Finally, a critical analysis of a selection of modifications is included, highlighting the most promising ones for this purpose in the future.

Pomegranate (Punica granatum L.) has long been recognised for its rich antioxidant profile and potential health benefits. Recent research has expanded its therapeutic potential to include antiangiogenic properties, which are crucial for inhibiting the growth of tumours and other pathological conditions involving aberrant blood vessel formation. This review consolidates current findings on the antiangiogenic effects of pomegranate extracts. We explore the impact of pomegranate polyphenols, including ellagic acid, punicalagin, anthocyanins, punicic acid and bioactive polysaccharides on key angiogenesis-related pathways and endothelial cell function. Emphasis is placed on the effects of these extracts as phytocomplexes rather than isolated compounds. Additionally, we discuss the use of pomegranate by-products, such as peels and seeds, in the preparation of extracts within a green chemistry and circular economy framework, highlighting their value in enhancing extract efficacy and sustainability. By primarily reviewing in vitro and in vivo preclinical studies, we assess how these extracts modulate angiogenesis across various disease models and explore their potential as adjunctive therapies for cancer and other angiogenesis-driven disorders. This review also identifies existing knowledge gaps and proposes future research directions to fully elucidate the clinical utility of pomegranate extracts in therapeutic applications.

Angiogenesis plays a critical role in both tumor progression and wound healing. This systematic review investigates the effect of pomegranate (Punica granatum, PG) extracts as both anti‐ and pro‐angiogenic agents in preclinical models of cancer and chronic wound healing (CWH), respectively. Following PRISMA guidelines, 14 studies (10 cancer, 4 CWH) were identified from PubMed, Scopus, and Google Scholar databases. In cancer models, PG extracts (juice, peel extract, seed oil) reduced vascular endothelial growth factor (VEGF) expression, and endothelial tube formation across multiple cancer types, with concomitant decrease in matrix metalloproteinases and inflammatory mediators. Conversely, in CWH models, topical PG peel extract applications enhanced VEGF expression and wound closure in diabetic and burn injuries. This dual angiogenic effect appears mechanistically linked to peroxisome proliferator‐activated receptor signaling pathways and synergistic interactions among PG polyphenols, particularly ellagitannins. Assessment of study quality revealed generally low risk of bias across in vitro studies, while animal studies demonstrated variable methodological rigor. Despite promising preclinical evidence, standardization of extraction methods, exploration of molecular mechanisms, and translation to clinical investigations remain critical research priorities. This comprehensive analysis validates PG extracts as a promising therapeutic strategy for both inhibiting pathological angiogenesis in cancer and promoting beneficial angiogenesis in CWH.