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.

Cannabis is one of the most commonly used recreational drugs worldwide. Rrecent epidemiology studies have linked increased cardiac complications to cannabis use. However, this literature is predominantly based on case incidents and post-mortem investigations. This study elucidates the molecular mechanism of Δ9-tetrahydrocannabinol (THC), and its primary metabolites 11-Hydroxy-Δ9-THC (THC-OH) and 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THC-COOH). Treatment of cardiac myocytes with THC-OH and THC-COOH increased cell migration and proliferation (p < 0.05), with no effect on cell adhesion, with higher doses (250–100 ng/mL) resulting in increased cell death and significant deterioration in cellular architecture. Conversely, no changes in cell morphology or viability were observed in response to THC. Expression of key ECM proteins α-SMA and collagen were up-regulated in response to THC-OH and THC-COOH treatments with concomitant modulation of PI3K and MAPK signalling. Investigations in the planarian animal model Polycelis nigra demonstrated that treatments with cannabinoid metabolites resulted in increased protein deposition at transection sites while higher doses resulted in significant lethality and decline in regeneration. These results highlight that the key metabolites of cannabis elicit toxic effects independent of the parent and psychoactive compound, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.