# Formulation of Boron Encapsulated Smart Nanocapsules for Targeted Drug Delivery to the Brain
## 1 Introduction  
The brain is the most complex and powerful organ in the human body. The organ is used to determine intelligence, as the interpreter of senses, as the initiator of body movements and the controller of behaviour. The brain is the source of all the qualities that define a person [1]. The human brain represents about 2% of the total body weight; however, it uses the same amount of energy as all the body's skeletal muscles when at rest [2]. The average human brain weighs around 1500 g with an approximate volume of 1350 cm\({}^{3}\), composed of almost 20 billion neurons [3]. Due to the importance of the brain, the body formed a system to protect this organ from damage that can be caused by potentially dangerous toxins. The blood-brain barrier (BBB) separates the blood from the extracellular fluid of the brain in the central nervous system (CNS) [4]. The BBB prohibits the entry of substances deemed to be harmful to the brain [5, 6]. The BBB presents three types of junctions, as described by [PERSON] et al. [7]. These are adherent junctions, tight junctions (TJs), and gap junctions. These barriers allow for restricted access of drugs to the brain. The BBB allows only small molecules such as water and some gases to enter via passive diffusion [8]. Larger molecules require a specialised transport system in order to permeate the BBB. Brain tumours, also known as tumours of the central nervous system (CNS), are the biggest killer of people under the age of 40 [9]; they represent a rare but serious health condition [10] with only 20% of sufferers surviving >5 years post-diagnosis [9]. It is estimated that the most common cases of cancer-related deaths occur due to the presence of malignant brain tumours in adolescents and young people between the age of 15 and 39, and it is the most common cancer present among 15-19-year-olds [11]. This year, nearly 17,000 people will lose their battle against primary malignant and CNS brain tumours [11]. Gliomas, a broad term used to describe tumour tissue growth within the gluey or supportive tissue of the brain, represent 27% of all brain tumours and 80% of all malignant tumours [11]. Nevertheless, the most common form of brain tumour is glioblastomas, as they represent 55.1% of all gliomas and 15.1% of all primary brain tumours [11]. Tumours of the CNS are characterized by the World Health Organization (WHO) based on the pathophysiological, epidemiological, and prognostic characteristics, and these are graded from I to IV. Those graded I are the least malignant tumours with higher long-term survival rates. Grade IV tumours are the most malignant and rapidly reproducing, forming new blood vessels to maintain rapid growth and thus having the poorest prognosis [12]. Research offers the only real hope of improvements in the management and treatment of brain tumours. Over 500 m is spent on cancer research in the UK every year, yet less than 2% is spent on brain tumours [9]. Currently, surgery plays a significant role in the treatment of gliomas and can prolong the life of the patient by up to 12-18 months [13]. Resection of glioblastoma multiforme (GBM) can be complicated by the lack of a defined tumour edge. Although magnetic resonance imaging (MRI) can allow better localization of the tumour, there is always uncertainty as to whether all malignant cells have been removed. Although the tumours of the brain have a slight tendency to metastasize to other organs of the body, they are highly infiltrative of the brain itself, and residual malignant cells can cause recurrence [14; 15; 16; 17]. Recent experimental evidence [18] has identified cancer stem cells (CSCs) as a sub-population that exhibits distinct cellular and genomic characteristics that render these cells capable of escaping radiotherapy- or chemotherapy-induced cell death by staying arrested over time at the G1/G0 cell growth phase. In turn, this allows them to re-enter the cell cycle under appropriate microenvironment conditions.