Send Orders for Reprints to reprints@benthamscience.net Current Nanomaterials 2019, 4, 000-000 1 REVIEW ARTICLE 2405-4615/19 $58.00+.00 © 2019 Bentham Science Publishers Lipid Based Nanoparticles: Current Strategies for Brain Tumor Targeting Bibhash C. Mohanta 1 , Narahari N. Palei 2,* , Vijayaraj Surendran 2 , Subas C. Dinda 3 , Jayaraman Rajan- gam 2 , Jyotirmoy Deb 4 and Biswa Mohan Sahoo 5 1 S. Chavan College of Pharmacy, Nellore, Andhra Pradesh, India; 2 Sree Vidyanikethan College of Pharmacy, Tirupati, Andhra Pradesh, India; 3 College of Health Sciences, Mekelle University, Mekelle, Ethiopia; 4 Department of Pharmacy, HUDA Group of Institution, Nagaon, Assam, India; 5 Department of Pharmacy, Vikas Group of Institution, Vijayawada, Andhra Pradesh, India Abstract: Brain tumors arise from an uncontrolled proliferation of neural tissue cells or supportive glial tissue cells within the brain. The diagnosis and therapy of brain tumor is an extremely challeng- ing task. Moreover, absence of early stage symptoms and consequently delays in diagnosis and thera- py worsen its severity. Though in the present days, chemotherapeutic approach is the most common therapeutic approach; still it is linked with several precincts. The blood-brain barrier (BBB) is the main hurdle in delivering most of the chemotherapeutic agents as well as imaging agent that leads to insufficient accumulation of therapeutic / imaging agents at tumor site, and prevents adequate destruc- tion of malignant cells. Recently, lipid based nanoparticles are gaining much more interest and are preferred over polymeric nanoparticles owing to their biodegradability, non-toxicity, excellent tumor- targeting ability and ease of surface modification. Certain receptors are over expressed in brain tumor cells which confer an opportunity to the researchers for delivering the chemotherapeutic as well as im- aging agent particularly to the tumor cells through the surface modification approach of nanoparticles. Ligands like proteins/peptides, carbohydrates, aptamers, antibodies, and antibody fragments are gen- erally conjugated to the surface of the nanoparticles that bind specifically to an over expressed target on the brain tumor cell surface. In the present review, we discuss the diagnostic and therapeutic appli- cation of various types of lipid based nanoparticles such as liposomes, niosomes, solid lipid nanoparti- cles, nanostructured lipid carrier, lipid nanocapsule, and lipid polymer hybrid nanocarriers along with their various surface modified forms for targeting brain tumor. A R T I C L E H I S T O R Y Received: November 23, 2018 Revised: January 31, 2019 Accepted: April 23, 2019 DOI: 10.2174/2405461504666190510121911 Keywords: BBB, brain tumor, lipid nanoparticles, chemotherapy, diagnosis. 1. INTRODUCTION 1.1. Brain Brain is the central organ of the nervous system and with spinal cord, it constitutes central nervous system (CNS). Human brain is considered as the most complex organ in the animal kingdom and consists of the brainstem, cerebrum, and the cerebellum [1]. The cerebrum is the largest part of the human brain and is divided into two cerebral hemi- spheres, covered by the cerebral cortex. The cerebrum car- ries out higher thought processes involved with language, learning, memory, and voluntary body movements [2]. The midbrain, the pons, and the medulla oblongata together con- stitute the brainstem which relays signals between the brain and spinal cord. The cerebellum is connected to the brain- stem by pairs of tracts known as peduncles and is responsible for balance and coordination [3]. The cells of the brain in- clude more than 86 billion neurons and a more or less equal *Address correspondence to this author at the Sree Vidyanikethan College of Pharmacy, Tirupati, Andhra Pradesh, India; Tel: +918374557445; E-mail: narahari.palei@gmail.com number of supportive glial cells. The whole circuitry of the brain is driven by the process of neurotransmission. Thus, the brain controls most of the body activities with scrupulous processing, integrating and co-ordinating the information received from the sensory organs [4, 5]. 1.2. Blood Brain Barrier (BBB) The BBB is a highly selective semipermeable membrane barrier constituted by specialized microvascular endothelial cells, basement membrane and glial cells (astrocytes, neu- rons, and pericytes) [6]. BBB separates the circulating blood from the brain extracellular fluid in the central nervous sys- tem (CNS). The endothelial cells, lining the brain capillaries form the tight junctions that limit the influx of harmful sub- stances including bacteria, lipophilic potential neurotoxins, xenobiotics and hydrophilic molecules from the blood to the brain [7]. Therefore, the blood vessels in microvascular en- dothelial cells show extremely high transendothelial electri- cal resistance (TEER) in vivo [8]. However, hydrophobic and other essential molecules (e.g. O 2 , CO 2 , glucose, hormones, etc.) are able to permeate either by passive diffusion or by active transport mechanism owing to the presence of pino-