Amphiphilic Based Lipid Nanocarriers in Drug Delivery System

Question: Discuss about theAmphiphilic Based Lipid Nanocarriers in Drug Delivery System. Answer: Background and Long-Term Objectives Poor penetration of the drugs with various compositions across the BBB (blood-brain barrier) is evident in the biomedical research. This impacted greatly the pharmaceutical interventions of various neurodegenerative disorders, brain tumours and impairment of the central nervous system (Gan et al., 2013). BBB is the main route for the therapeutic compounds targeted to the brain. But, majority of the neuro medicines, transporter ligands and hydrophilic molecules have less permeability across this region. Nanocarriers, especially amphiphilic based lipid nanocarriers provide unlimited therapeutic potential (Nicolas et al., 2013). Hence, this research would design and test the effectiveness of biodegradable nanocarriers that can carry both hydrophobic and hydrophilic drug components. Various drug delivery approaches have been designed in order to overcome BBB, for instance: modification of BBB functions, circumvention of BBB and modification of drug molecules. Invasive strategies used for drug delivery like intracerebral or intraventricular drug administration are highly effective in avoiding BBB. But, these processes also include certain limitations like infection risks (Kumari, Yadav Yadav, 2010). In case of non-invasive strategies such as drug administration via nasal pathway is also effective but limited distribution and low amount of drug delivery are the identified two major drawbacks (Yavlovich et al., 2010). In the present era, different nanotechnology platforms in medial biology field have obtained remarkable attention including both therapies and diagnostics. Innovatively designed multifunctional nanoparticles as drug carriers have impelled exponential development in medicinal application. The designs include liposomes, antibody-drug conjugates, dendrimers, and so on, which are based on exceptional assemblies of biological, natural or synthetic components. Mechanisms There are various types of targeting mechanisms demonstrated by the nanocarriers, like: active targeting, passive targeting, temperature specificity and pH specificity. Passive targeting is said to be the process where the nanocarriers travel down to a targeted system, suppose a tumour vascular system, become entrapped and accumulate within the target cells (Mura, Nicolas, Couvreur, 2013). The accumulation happens due to increased retention effect and permeability. Active targeting includes incorporation of target molecules like antibodies or ligands on the nanocarrierss surface, which are particular to certain cells of the system. Nanocarriers have higher ratio of surface area to volume that allow various ligands to attach to the surfaces (Nicolas et al., 2013). The targeting molecules allow the nanocarriers to penetrate directly across the cells. Certain nanocarriers only release drugs, which have specific pH ranges. The specificity of pH allows the nanocarriers to release drugs d irectly into the target site. Nanocarriers, which only liberate drugs at particular pH could therefore be applied to further release drugs in acidic environment. Some nanocarriers deliver drugs at particular temperature. It is evident that temperature of the tumour cells are higher (almost 40c) comparative to the rest of the system, which further enable to safeguard drug delivery at tumour-specific site. Recent Progresses and Specific Hypotheses Efflux pumps and interendothelial tight junctions are recognized as major limiting functions of the BBB that restrict drug penetration to the brain (Li et al., 2011). Hence, functional modification of the BBB is presently investigated. Drug penetration testing was done under strict ethical consideration that used cell culture model. Niosomes from the non-ionic surfactants have been designed that present amino acids, glucose analogues and BBB carrier ligands within the surfaces. Tissue distribution of the niosomes was assessed by using an in-vivo imaging system. The tissue was stained with Evans blue, an azo dye. Hypothesis: The amphiphilic based lipid nanocarriers are effective in drug delivery across the BBB by targeting the brain. Short-Term Goal of this Research Study: To alter the physio-chemical properties of the drug delivery molecules by increasing cationic charge or lipid solubility Maximization of lipid solubility could improve transport of a drug across BBB. This in turn could increase the uptake by the peripheral tissues. Further, sequestration within the capillary bed causes reduced concentration within the blood and the CNS. Non-ionic surfactant depended nanocarriers could demonstrate a versatile system. The size of the nanocarriers could be approximately between 50-200nm that have the capacity to entrap comparatively large amount of lipophilic and hydrophilic therapeutic agents. Such amphiphilic based lipid nanocarriers could protect encapsulated drugs from the gastrointestinal breakdown. These nanocarriers could be targeted in the brain by the surface alteration with the ligands for receptor proteins or BBB transporter. Nanocarriers that target the BBB receptors and physiological transporters can cross the endothelial cell layers of the brain. Long-Term Goals: Objective 1: To understand the mechanism of BBB (year 1 to 2) Transient rise of the permeability of BBB pathways and modifying efflux pump could improve drug delivery. Side-effects, safety and reversibility would be monitored continuously. BBB itself could act as the CNS drug source. If BBB becomes leaky, it allows immune cells entry to the CNS. Nevertheless, the immune cell passage across BBB is regulated and leakage acts as byproduct of the immune cells trafficking. The luminal surface does not necessitate passage across BBB and thereby, targeting peripheral tissues are highly effective to almost half of BBB. The luminal receptors, which stimulate endothelial cells of the brain are readily targetable. Objective 2: To understand uptake and diffusion of various nanocarriers along with ligand-receptor combinations across BBB (year 1 to 2) It is seen that intravenously administered niosomes that contain glucose analogue provide high fluorescent signals as a ligand within the brain tissue (Mura, Nicolas, Couvreur, 2013). This could be compared and checked in living mice model by incorporating non-targeted niosomes. Simultaneously, other forms of targeted nanocarriers like polymeric nanoparticles or liposomes could also be checked by using cell culture models of BBB. These nanocarriers would contain therapeutic drugs for instance curcumin as a load and would be introduced to various ligands, which would be attached to the surface in order to target receptors or BBB transporters. Impact of Proposed Research The incorporation of medicine and nanotechnology has given rise to major advancements, which have further improved medication administration of various diseases. The application of amphiphilic based lipid nanocarriers would improve delivery of drug to the brain by smoothly crossing the BBB. As medicinal transformation is becoming more advanced, utilization of amphiphilic based lipid nanocarriers would change and invalidate conventional treatment criteria. However, the researchers should be careful enough about reversibility, safety and side-effects of the innovative applications. References Gan, L., Wang, J., Jiang, M., Bartlett, H., Ouyang, D., Eperjesi, F., Gan, Y. (2013). Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers.Drug discovery today,18(5), 290-297. Kumari, A., Yadav, S. K., Yadav, S. C. (2010). Biodegradable polymeric nanoparticles based drug delivery systems.Colloids and Surfaces B: Biointerfaces,75(1), 1-18. Li, X., Qian, Y., Liu, T., Hu, X., Zhang, G., You, Y., Liu, S. (2011). Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging.Biomaterials,32(27), 6595-6605. Mura, S., Nicolas, J., Couvreur, P. (2013). Stimuli-responsive nanocarriers for drug delivery.Nature materials,12(11), 991-1003. Nicolas, J., Mura, S., Brambilla, D., Mackiewicz, N., Couvreur, P. (2013). Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery.Chemical Society Reviews,42(3), 1147-1235. Yavlovich, A., Smith, B., Gupta, K., Blumenthal, R., Puri, A. (2010). Light-sensitive lipid-based nanoparticles for drug delivery: design principles and future considerations for biological applications.Molecular membrane biology,27(7), 364-381.