No abstract

The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone. The molecular weight distribution of the synthesized polymers was determined using size exclusion high performance liquid chromatography and was found to be in range of the parent CS polymer (~50 kDa). The critical micelle concentration (cmc) of the polymers was determined using pyrene as a fluorescent probe. The cmc was found to decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid-g-CS polymers self-assembled in an aqueous environment to form nanomicelles of ~200 nm particle size and slightly positive net charge due to the cationic nature of free primary amino groups on CS molecule. These polymeric nanomicelles exhibited excellent hemo-and cytocompatibility, as evaluated by in vitro hemolysis and MTT cell viability assay, respectively, and showed superior transfection efficiency compared to unmodified chitosan and naked DNA. The surface of these nanomicelles can be further modified with ligands allowing for selective targeting, enhanced cell binding, and internalization. These nanomicelles can thus be exploited as potential nonviral gene delivery vectors for safe and efficient gene therapy.

Alzheimer’s disease (AD), the most common cause of dementia, inflicts enormous suffering to patients and their family members. It is the third deadliest disease, affecting 46.8 million people worldwide. Brain-derived neurotrophic factor (BDNF) is involved in the development, maintenance, and plasticity of the central nervous system. This crucial protein is significantly reduced in AD patients leading to reduced plasticity and neuronal death. In this study, we demonstrate the targeted delivery of the BDNF gene to the brain using liposome nanoparticles. These liposomes were surface modified with glucose transporter-1 targeting ligand (mannose) and cell penetrating peptides (penetratin or rabies virus glycoprotein) to promote selective and enhanced delivery to the brain. Surface modified liposomes showed significantly higher transfection of BDNF in primary astrocytes and neurons, compared to unmodified (plain) liposomes. BDNF transfection via dual modified liposomes resulted in an increase in presynaptic marker synaptophysin protein in primary neuronal cells, which is usually found to be reduced in AD patients. Liposomes surface modified with mannose and cell penetrating peptides demonstrated ∼50% higher transport across the in vitro blood brain barrier (BBB) model and showed significantly higher transfection efficiency in primary neuronal cells compared to plain liposomes. These results were correlated with significantly higher transport of surface modified liposomes (∼7% of injected dose/gram of tissue) and BDNF transfection (∼1.7 times higher than baseline level) across BBB following single intravenous administration in C57BL/6 mice without any signs of inflammation or toxicity. Overall, this study suggests a safe and targeted strategy to increase BDNF protein in the brain, which has the potential to reverse AD pathophysiology.

No abstract

The literature addresses a large number of studies in regard to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary before topical botanical agents can be consistently recommended to patients.