Novel Central Nervous System Drug Delivery Systems

Abstract

For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease

“…That is why many studies focus on designing different drug delivery systems to enhance the release of these proteins into the brain tissue, either through invasive or noninvasive methods. 31,32 Considerable attention has been paid to the improvement of PLGA nanoparticles, making the local delivery of neuroprotective agents into the brain possible. In fact, PLGA NS can preserve the encapsulated unstable therapeutic drug from enzyme degradation, release the drug in a controlled and continuous manner, enhance its biodistribution, and permit drug targeting.…”

Nanocarrier drugs in the treatment of brain tumors

“…[51] Metal nanoparticles are also frequently integrated with other techniques such as microwaveinduced hyperthermia to further increase their cellular transduction. [52] The α-helical right handed coiled coils associated with platinum (PtIV) compound showed higher toxicity to human malignant glioma cells compared with free Pt(IV) in vitro and in vivo, without affecting healthy astrocytes in vitro. [53] Carrier-mediated transport (CMT) can transport small molecules from the blood to the brain.…”

Dynamic and Responsive Growth Factor Delivery from Electrospun and Hydrogel Tissue Engineering Materials

“…The delivery site is another major consideration, as drugs can have negative side effects to nontarget tissues. [22] In an effort to control drug dosage, maximize delivery, and reduce cytotoxicity, the targeted delivery of drugs to the site of therapeutic need is an area of intense research focus. [22] Delivery and targeting methods are becoming increasingly specific.…”

“…[22] In an effort to control drug dosage, maximize delivery, and reduce cytotoxicity, the targeted delivery of drugs to the site of therapeutic need is an area of intense research focus. [22] Delivery and targeting methods are becoming increasingly specific. For example, some methods of chemotherapeutic drug delivery involve shielding cytotoxic drugs so they can be introduced systemically into the blood stream, and designing the shielding to undergo localized and selective release only around cancerous cells based on specific indicators such as pH or overexpression of particular proteins.…”

“…This is particularly advantageous for regeneration of tissues shielded from the blood stream, such as the brain, which is protected from systemic drug delivery by a highly selective membrane called the blood brain barrier (BBB). [22] Sustained and controlled delivery to the brain can be achieved using intracerebroventricular infusion or micropumps; however, this is very invasive and causes significant tissue damage so much research has focused on using tissue engineering scaffolds as growth factor delivery vehicles as well. [13,24] Tissue engineering materials can be used as a reservoir for sustained and controlled drug delivery as in many instances they are engineered to be minimally invasive (i.e., shear thinning hydrogels) and their inherent biocompatibility means that they can be implanted for long durations.…”