Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women's physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.

Therapeutic biomacromolecules such as genetic material, antibodies, growth factors and enzymes represent a novel therapeutic alternative for neurological diseases and disorders. In comparison to traditional therapeutics, which are mainly based on small molecular weight drugs that address the symptoms of these disorders, therapeutic biomacromolecules can reduce undesired side effects and target specific pathological pathways, thus paving the way towards personalized medicine. However, these biomacromolecules undergo degradation/denaturation processes in the physiological environment and show poor capacity to cross the blood-brain barrier (BBB). Consequently, they rarely reach the central nervous system (CNS) in their active form. Herein, we critically overview several polymeric nanocarriers that can protect and deliver therapeutic biomacromolecules across the BBB. Polymeric nanocarriers are first categorized based on their architecture (biodegradable solid nanoparticles, nanogels, dendrimers, self-assembled nanoparticles), that ultimately determines their physico-chemical properties and function. The available polymeric formulations are then thoroughly analyzed, placing particular attention on those strategies that ensure the stability of the biomacromolecules during their encapsulation process and promote their passage across the BBB by controlling their physical (e.g., mechanical properties, size, surface charge) and chemical (e.g., surface functional groups, targeting motifs) properties. Accordingly, this review gives a unique perspective on polymeric nanocarriers for the delivery of therapeutic biomacromolecules across the BBB, representing a concise, complete and easy-to-follow guide, which will be of high interest for chemists, material scientists, pharmacologists and biologists. Besides, it also provides a critical perspective about the limited clinical translation of these systems. STATEMENT OF SIGNIFICANCE: The increasing incidence of central nervous system disorders is a major health concern. The use of therapeutic biomacromolecules has been placed in the spotlight of many investigations. However, reaching therapeutic concentration levels of biomacromolecules in the central nervous system is restricted by the blood-brain barrier and, thus, this represents the main clinical challenge when developing efficient therapies. Herein, we provide a critical discussion about the use of polymeric nanocarriers to deliver therapeutic biomacromolecules into the central nervous system, highlighting potential future directions to overcome the current challenges.

We provide evidence for the presence of cannabinoid CB₂ receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB₂ receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB₂ receptors in this study. An up-regulation of CB₂ gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB₂ receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.