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Recent Advances with Targeted Liposomes for Drug Delivery
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Josimar O. Eloy, Raquel Petrilli, Fabíola Silva Garcia Praça, Marlus Chorilli
Drug delivery to the brain mediated by immunoliposomes has been recently studied and the biggest challenge is to cross the blood-brain barrier. Loureiro and collaborators in 2015 developed liposomes with dual targeting, using both anti-transferrin receptor antibody, to help cross the blood-brain barrier, and anti-amyloid beta peptide antibody, for Alzheimer’s disease targeting. Very importantly, it was demonstrated, in vivo, the ability of the immunoliposomes to cross the blood-brain barrier (Loureiro et al., 2015). More recently, another group developed immunoliposomes targeted with the anti-amyloid β antibody, which, in vivo, were able to reduce the levels of circulating amyloid β in aged, but not in adult mice (Ordóñez-Gutiérrez et al., 2016). Finally, another interesting application of targeting against Alzheimer’s disease was the use of immunoliposomes, which were successfully employed for imaging amyloid β in transgenic mice using the technique of time-of-flight secondary ion mass spectrometry (Carlred et al., 2016).
Nanoemulsions in Non-Invasive Drug Delivery Systems
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Ratna Jyoti Das, Subhabrata Ray, Paulami Pal, Anup Kumar Das, Bhaskar Mazumder
Central nervous system (CNS) diseases including schizophrenia, migraine, meningitis, Parkinson’s disease, and Alzheimer’s disease need drug delivery into the brain for treatment. However, such transport is challenging and problematic, especially for water-soluble drugs and drugs with a large molecular weight due to the impervious nature of the endothelial membrane partitioning the systemic circulation system and central interstitial fluid, the blood–brain barrier (Pardridge, 1999). Therefore, several medicaments may have been abandoned because sufficient drug concentration in the brain could not be achieved. “Biologics” are too big and hydrophilic to penetrate the blood–brain barrier and will be rapidly disrupted by GI enzymes/liver cytochromes if they are orally administered. A non-invasive therapy will be needed for patients requiring chronic dosing, as in dementia therapy. Animal and human investigations have shown that exogenous material transport directly from the nose-to-brain is a potential route for avoiding the blood–brain barrier (Illum, 2000). The route consists of the olfactory or trigeminal nerve systems that initialize in the brain and are terminated in the nasal cavity at the olfactory neuroepithelium or respiratory epithelium respectively. These are indeed the only externally exposed portions of the CNS and hence represent the straightest method of non-invasive penetration into the brain. However, drug solutions administered nasally that have been demonstrated to be transported directly from the nose-to-brain are too low in quantity, generally not more than 0.1%, and therefore are not suitable for use as therapeutics and no product is licensed specifically via this route (Illum, 2004). A nanoemulsion vaccine may be useful in that case. Figure 6.9 shows the mechanism of action of nanoemulsion vaccines.
Applications of Nanocarriers in Emerging and Re-Emerging Central Nervous System Tropical Infections
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Nanocarriers for Brain Targeting, 2019
The use of novel carriers to help drug crosses the blood-brain barrier is the exact application of advanced pharmaco-biotechnology in clinical neurology (Hersh et al., 2016). Patel et al. (2009) noted for several new possible strategies that might increase drug delivery into the brain include chemical delivery systems (lipid-mediated transport, the prodrug approach, and the lock-in system) and new biological delivery systems, in which are re-engineered to cross the blood-brain barrier via new specific endogenous transporters localized within the barrier. The use of nanocarrier is a good example of an attempt to use applied nanotechnology to serve as a new chemical delivery system. The nanoparticle- and liposome-carried drugs can be effective because there are an increased cellular uptake and reduced efflux through ATP-binding cassette transporters, which plays role in reducing drug entry (Pinzón-Daza et al., 2013). Gabathuler (2010) noted that the novel carrier might be effective for increasing the transport of therapeutics from the blood into the brain parenchyma. Wohlfart et al. (2012) reported that the mechanism that nanocarrier carries the drug into the brain “appears to be receptor-mediated endocytosis in brain capillary endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants enabling the adsorption of specific plasma proteins are necessary for this receptor-mediated uptake.” After successfully enter, the nanoparticle will be further diffused to targeted brain interior or maybe transcytosed (Kreuter, 2001). Using novel nanocarriers for drug delivery is a new technology and emerging concept to overcome the blood-brain barrier and it is the present new alternative drug delivery strategies targeting brain (Hersh et al., 2016). For example, Grabrucker et al. (2016) noted that using nanocarriers can help manage several brain diseases including to Alzheimer, Parkinson and Huntington’s disease. Focusing on tropical disease, especially for infections, there are also some interesting reports which will be further summarized and discussed in this chapter.
Numerical analysis of enhanced nano-drug delivery to the olfactory bulb
Published in Aerosol Science and Technology, 2021
Shantanu Vachhani, Clement Kleinstreuer
The Blood Brain Barrier (BBB) located above the olfactory bulb (Figure 1), a highly selective semipermeable membrane, protects the fragile nature of the brain and separates the olfactory region of the nasal cavity from the brain. The presence of tight junctions between the adjacent endothelial cells (Figure 2) allow only very small compounds to pass through (Azad et al. 2015; Burgess and Hynynen 2013). Furthermore, the cerebral endothelial cells show a considerably less pinocytic activity than the systemic endothelium (Lesniak and Brem 2004). Pinocytic activity results in the transportation of substances across an epithelium by material-uptake on one face of a coated vesicle that can then be transported from the opposite face. Clearly, the reduction in the pinocytic activity further limits the drug transportation across the BBB. The blood cerebrospinal fluid barrier (BCSFB) forms the second layer that restricts the movement of drugs. This layer is located at the choroid plexus and separates the blood and the cerebrospinal fluid. However, this layer is slightly more permeable than the BBB. The BBB surface area (120 sq ft) is roughly 5000 times the area of the BCSFB (Pajouhesh and Lenz 2005). Hence, BBB layer is the dominant obstacle for the delivery of drugs to the brain. These membranes are there to inhibit the passage of pathogens, antibodies, toxins etc. to the brain. In doing so they also restrict the transport of therapeutic drugs in to the brain. In summary, drug delivery to the brain is difficult to achieve at high enough efficiencies to counteract the toxins that are the root to the various CNS disorders (Agrawal et al. 2018).