Reatul Karim

Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art

Glioblastoma multiforme, a grade IV glioma, is the most frequently occurring and invasive primary tumor of the central nervous system, which causes about 4% of cancer-associated-deaths, making it one of the most fatal cancers. With present treatments, using state-of-the-art technologies, the median survival is about 14 months and 2 year survival rate is merely 3-5%. Hence, novel therapeutic approaches are urgently necessary. However, most drug molecules are not able to cross the blood-brain barrier, which is one of the major difficulties in glioblastoma treatment. This review describes the features of blood-brain barrier, and its anatomical changes with different stages of tumor growth. Moreover, various strategies to improve brain drug delivery i.e. tight junction opening, chemical modification of the drug, efflux transporter inhibition, convection-enhanced delivery, craniotomy-based drug delivery and drug delivery nanosystems are discussed. Nanocarriers are one of the highly potential drug transport systems that have gained huge research focus over the last few decades for site specific drug delivery, including drug delivery to the brain. Properly designed nanocolloids are capable to cross the blood-brain barrier and specifically deliver the drug in the brain tumor tissue. They can carry both hydrophilic and hydrophobic drugs, protect them from degradation, release the drug for sustained period, significantly improve the plasma circulation half-life and reduce toxic effects. Among various nanocarriers, liposomes, polymeric nanoparticles and lipid nanocapsules are the most widely studied, and are discussed in this review. For each type of nanocarrier, a general discussion describing their composition, characteristics, types and various uses is followed by their specific application to glioblastoma treatment. Moreover, some of the main challenges regarding toxicity and standardized evaluation techniques are narrated in brief.

Development and evaluation of injectable nanosized drug delivery systems for apigenin

The purpose of this study was to develop different injectable nanosized drug delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric nanocapsule (PNC) encapsulating apigenin (AG) and compare their characteristics to identify the nanovector(s) that can deliver the largest quantity of AG while being biocompatible. Two liposomes with different surface characteristics (cationic and anionic), a LNC and a PNC were prepared. A novel tocopherol modified poly(ethylene glycol)-b-polyphosphate block-copolymer was used for the first time for the PNC preparation. The NDDSs were compared by their physicochemical characteristics, AG release, storage stability, stability in serum, complement consumption and toxicity against a human macrovascular endothelial cell line (EAhy926). The diameter and surface charge of the NDDSs were comparable with previously reported injectable nanocarriers. The NDDSs showed good encapsulation efficiency and drug loading. Moreover, the NDDSs were stable during storage and in fetal bovine serum for extended periods, showed low complement consumption and were non-toxic to EAhy926 cells up to high concentrations. Therefore, they can be considered as potential injectable nanocarriers of AG. Due to less pronounced burst effect and extended release characteristics, the nanocapsules could be favorable approaches for achieving prolonged pharmacological activity of AG using injectable NDDS.

DRUG DELIVERY NANOCARRIERS TO CROSS OF THE BLOOD-BRAIN BARRIER

Abstract Blood–brain barrier (BBB) is a brain protective structure composed by endothelial cells, astrocytes and pericytes characterized by specific transport systems expressed on their surface. Moreover, the tight junctions, in the paracellular space, and the adherens junctions, in the basolateral space of the endothelial cells create a physical barrier hardly crossable from the most part of common drugs. Despite the BBB is vital for the central nervous system (CNS), it restricts drug delivery to this tissue. To overcome this obstacle many drug delivery systems (DDS) have been developed. Polymeric nanocarriers, solid lipid nanocarriers (SLN) and liposomes are developed to deliver drugs otherwise not able to pass the BBB, due to their physico-chemical characteristics. Besides their capacity to pass biological barriers, the potential advantages of nanocarriers are their capability to load a high quantity of drug with low cytotoxicity.In recent years many diverse scientific strategies have been developed for cancer therapy. One of the most unique research areas is nanotechnology that is related to synthesis, manipulation of nanomaterials, and their application in cancer diagnosis and therapy. Multifunctional nanoparticles can be prepared for different biomedical applications that can carry and deliver small molecules (dyes or chemotherapeutic drugs) to target, detect, and treat. A well-established nanomaterial can enhance the efficiency of drug delivery to reach pathological areas by decreasing their toxicity and side effects. Small molecules can be conjugated to nanomaterials using different chemical linkages that can be released by biodegradation and self-regulation of nanomaterials. In this chapter, we introduce the design and characterization of various nanomaterials for drug delivery to treat cancer in vitro and in vivo.