Injectable nanogel systems for brain drug delivery

Abstract

The central nervous system (CNS) controls many critical functions, such as intelligence, emotion, sense, and memory, and modulates many other functions of the entire human body. Diseases affecting the CNS are challenging to treat because of the CNS’s sensitive functional and structural features and limited accessibility. The brain is secured from the systemic circulation by a unique biological fence, the blood-brain barrier (BBB), that limits molecular exchange between the peripheral and CNS systems. Most drugs used for treating CNS diseases fail to reach the brain in effective therapeutic concentrations due to the presence of BBB. During the last decade, specifically engineered drug delivery systems (DDS) have offered the opportunity to overcome systemic barriers in brain drug delivery. However, even with the best-engineered nano-carriers, delivering sufficient drug doses into the brain through systemic circulation remains challenging. Here, we review various systems for ‘direct’ drug delivery to the brain using im-plantable or injectable intracranial nano-drug delivery systems (nDDS), which can ensure 100% release of drug to the brain in a sustained or controlled fashion for prolonged periods, bypassing the BBB, thereby radically improving the therapeutic efficacy while minimizing systemic toxicity. Brain injectable nanogels or nanoparticle systems can be considered superior compared to other local drug-delivery systems because they possess better diffusivity of drugs. The nanogels can be injected through minimally invasive procedures, precisely delivering drugs to specific target sites. This review covers a detailed discussion about locally injectable DDS and various nanogel-based drugs, oligonucleotide, and theragnostic delivery systems used for treating brain malignancies, infections, and neurodegenerative diseases.