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Modelling and Simulation of Nanosystems for Delivering Drugs to the Brain
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Tânia F. G. G. Cova, Sandra C.C. Nunes
Wu et al. [71] used MD to evaluate the potential of propionylated amylose to encapsulate hydrophobic drugs and release them by the interaction with POPE at concentrations similar to those found in the BBB. The release was promoted by the unfold of the helical structure of the amylose-hydrophobic drug complexes (see Scheme 1 in Ref. [71]). As hydrophobic model drug for the CNS the authors used propofol. The results showed that the nanoclusters exhibited high BBB permeability and specificity, rapid onset, short maintenance, quick recovery and reduced dosage. MD was used to inspect (i) drug encapsulation, (ii) the effect of propionylation on the stability of amylose-drug complexes and (iii) the release of propofol triggered by POPE solution, POPE and POPC bilayers. Results indicated that when nanoclusters contact with the membrane mimicking the BBB the helix unfolds and release the loaded drug, which crosses the BBB.
Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
Johnston and Feldman et al. prepared a gold-coated iron oxide nanoparticle for photothermal therapy [824]. Au nanoclusters were formed by reduction of HAuCl4 onto the surfaces of 5 nm iron oxide nanoparticles coated with hydroxylamine as a seeding agent. Macrophages are implicated in every stage of atherosclerosis from lesion initiation to plaque rupture and clinical presentation [825]. Tumor-associated macrophages also play an important role in promoting tumor growth, invasion, metastasis, and angiogenesis [826, 827]. Macrophage targeting via administration of NIR-sensitive nanoparticles may enhance diagnosis and therapy for cancer. The targeted uptake of nanoclusters for enhancement of cellular imaging and photothermal effect was investigated with primary peritoneal macrophages, which were isolated from C57/BL6 mice that can develop the M2 phenotype associated with cancer. A monolayer of Au-nanostructure-targeted macrophages was irradiated with a 755 nm laser pulse of 50 ns duration and a 2 mm spot size. A temperature increase of 0.7°C over the 2 mm spot was observed, indicating a strong absorbance by the Au-iron oxide nanocomposites. The actual temperature increase, immediately adjacent to the small nanocluster, should be substantially larger than this temperature increase and can be advantageously used for hyperthermal treatment of cancer cells.
Cancer Nanotheranostics
Published in Richard L. K. Glover, Daniel Nyanganyura, Rofhiwa Bridget Mulaudzi, Maluta Steven Mufamadi, Green Synthesis in Nanomedicine and Human Health, 2021
Maluta Steven Mufamadi, Marian Jiya John, Mpho Phehello Ngoepe, Palesa Rose Sekhejane
Many studies have demonstrated cancer nanotheranostics employing green synthesized metallic nanoparticles, nanoparticles synthesized using plant extracts and biomolecules in vitro (Gao et al., 2014; Mukherjee et al., 2014; Ge et al., 2015; Ovais et al., 2016; Hameed et al., 2019). Ge et al. (2015) has reported green or biological synthesis of fluorescent Au/Ce nanocluster/nanoparticles employing glutathione as a reducing and stabilizing agent during the synthesis. The results showed Au/Ce nanocluster to be highly sensitive bio-imaging agents with high fluorescence intensity. In vitro bio-imaging was observed in the HeLa and HepG2 cancer cell lines, and in vivo bio-imaging was observed in the solid tumour mouse model of cervical carcinoma. A similar study by Gao et al. (2014) showed near-infrared fluorescence imaging and anticancer activity in vitro in HeLa cancer cells and in vivo in a tumour mouse model of cervical carcinoma employing green synthesized silver nanoclusters/nanoparticles using glutathione. Mukherjee et al. (2014) demonstrated the theranostics potential of green synthesized AgNPs using Olax scandens leaf extract with spherical shape and particle size of 20–60 nm. The study introduced for the first time multifunctional biological activities, 4-in-1 system of green synthesized AgNPs. The green synthesized AgNPs 4-in-1 system implies (i) anticancer activity, (ii) antibacterial activity, (iii) biocompatibility/non-toxic drug delivery vehicle and (iv) diagnostic/bio-imaging system. Hameed et al. (2019) showed the theranostics potential of using green synthesized ZnO-NPs with plant extracts.
High concentration formulation developability approaches and considerations
Published in mAbs, 2023
Jonathan Zarzar, Tarik Khan, Maniraj Bhagawati, Benjamin Weiche, Jasmin Sydow-Andersen, Alavattam Sreedhara
Other viscosity-lowering approaches use the formation of nanoclusters or microparticles that restrict the viscosity effects to interparticle interactions, rather than intermolecular interactions. This approach creates two separate dominant forms of molecular interactions, those within the particles, which do not have a major influence on viscosity, and between the surfaces of the particles, which is less than that of soluble monomers. In one example, nanoclusters were formed by lyophilizing a mAb formulation containing trehalose as a crowding agent and reconstituting it in a buffer close to the mAb’s isoelectric point using a lower volume than the pre-lyophilization volume. This induced macromolecular crowding and led to the formation of nanoclusters that revert back to monomer upon injection.29,30 Other particle-based technologies, using techniques such as electrospraying and microglassification offered by companies like Elektrofi and Lindy Biosciences, claim concentrations >400 mg/mL may be reached. However, these microparticle approaches may require substantial process development and require the use of non-aqueous solvents for the DP to be administered.
Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design
Published in Toxicology Mechanisms and Methods, 2019
Ajay Vikram Singh, Peter Laux, Andreas Luch, Chaitanya Sudrik, Stefan Wiehr, Anna-Maria Wild, Giulia Santomauro, Joachim Bill, Metin Sitti
There is a surface charge associated with nanoparticles. When they are suspended in solution they have a double layer that keeps them stable and repels them from each other and allows them to remain individual. If the particle is negatively charged, it is going to be attracted to positively charged surfaces and vice versa (Figure 4(C)). Surface charge is one of the primary criterions which determines how the nanoparticles interact with biological subsystems or membranes in the aqueous environment. In this context, positive nanoparticles are more toxic than negative ones, therefore ammonium compounds are typically used as antimicrobial substances (Alvarez-Paino et al. 2017). Being positively charged, they are easily attracted to the negatively charged membrane of bacteria. Once attached to the membrane, they damage the bacterial membrane and interact with bacterial enzymes, proteins, and DNA (Hasan et al. 2013). In biological systems, most of the surfaces are negatively charged and so a positively charged particle can actually stick or interact with the element of interest, typically increasing the probability of uptake. Particularly, silver nanoclusters releasing silver ions locally to the surface can induce a higher level of toxicity (Dobias and Bernier-Latmani 2013). Silver is relatively dynamic. It has a dissolution constant in water. In the case of silver or also copper, ions are toxic because of the constant ion release to the local environment, which potentially affects the biological environment around them.
Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases
Published in Expert Review of Vaccines, 2020
GNPs have been used to prepare antibodies and vaccines against more than 45 pathogens of viral, bacterial, and parasitic infections. The sizes of the GNPs used for this purpose have ranged from 2 to 100 nm. Moreover, in most studies, particle diameters ranging from 15 to 50 were recognized as optimal. Variously shaped GNPs have been used, including nanospheres, nanorods, nanocages, nanostars, nanocubes, nanoshells, nanoprisms, and nanoclusters. Most researchers have indicated that the best effect is achieved with gold nanospheres as antigen carriers.