The group of calcium channel blockers derived from dihydropyridine, for example, is characterized by its low oral BA due to its low water solubility and high rate of first-pass metabolism. Quercetin-loaded solid lipid nanoparticle dispersion with improved physicochemical properties and cellular uptake. 5, 137–145. Recent advances in the development of nanocarriers have started a new era in Formulation Science. Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides. Control. Keywords: Lipospheres in Drug Targets and Delivery: Approaches, Methods, and Applications presents an overview of the most recent applications of lipospheres primarily in the field of medicine, pharmaceutics, and biotechnology. Nanoparticulate Drug Delivery Systems addresses the scientific methodologies, formulation, processing, applications, recent trends, and e Pharm. B., Dyck, P. J., Litchy, W. J., Leahy, R. G., Chen, J., et al. Appl. Release 197, 48–57. (2017). 43, 1205–1214. 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The presence of interactions among factors and their magnitude can only be studied by means of designs of several crossed factors, such as those mentioned before, being insufficient the individual or univariate optimization of the responses in function of each process attribute or parameter (Montgomery, 2017). Mazuryk, J., Deptuła, T., Polchi, A., Gapiński, J., Giovagnoli, S., Magini, A., et al. B., Dyck P. J., Litchy W. J., Leahy R. G., Chen J., et al. Front. doi: 10.2217/nnm-2018-0417, Wang, Q., Yang, Q., Cao, X., Wei, Q., Firempong, C. K., Guo, M., et al. 31:e1805730. Mol. Another characteristic of the BBB is the expression of efflux transporters of the ABC (ATP-binding cassette) superfamily, transmembrane proteins responsible for pumping xenobiotics or toxic substrates out of the intracellular space, avoiding their access to the CNS since they are localized almost exclusively at the luminal membrane of the endothelial cells (Pardridge, 2020). Development, characterization and antimalarial efficacy of dihydroartemisinin loaded solid lipid nanoparticles. 80. LNPs became more widely known in late 2020, as some COVID-19 . Drug Dev. doi: 10.1016/j.ijpharm.2017.04.034, Kovačević, A. Solid lipid nanoparticles for the treatment of Parkinson's disease. doi: 10.1039/c9nj01634a, Cavaco, M. C., Pereira, C., Kreutzer, B., Gouveia, L. F., Silva-Lima, B., Brito, A. M., et al. 4, 923–931. It is a measure of the surface charge of the particle, and thus it is directly related to the charge exhibited by the lipid or surfactant of the nanosystem, at the pH value of the formulation (Cheng and Lee, 2016). Montgomery, D. C. (2017). doi: 10.1016/S1470-2045(17)30698-8, Jain, A. K., and Thareja, S. (2020). It has been proposed that encapsulating a drug into a NP may help to bypass these transporters (Cavaco et al., 2017; Sadegh Malvajerd et al., 2019). Nanomaterials 10:1353. doi: 10.3390/nano10071353. Nat. 54, S131–S155. (1993)]. The purpose of this study was to develop Pickering O/W nano-emulsions only stabilized by solid lipid nanoparticles (SLNs), as a new generation of safe, non-toxic, biocompatible, and temperature-sensitive lipid nano-carriers. Both administration routes seek to achieve systemic effects of the encapsulated drugs, but the trend described is opposite to the current distribution of pharmaceutical products in the market, where the oral route of administration is the preferred and most widely used route for drug administration. The authors observed that those NPs coated with MePEG of the same molecular weight, showed a higher distribution half- life as the size decreased. In silico drug discovery strategies, high throughput screening methodologies and the more classical lead-optimization programs tend to favor compounds with higher pharmacological potency, in detriment of other properties that may be desirable from a physicochemical or pharmacokinetic point of view. Apo E-functionalization of Solid Lipid Nanoparticles enhances brain drug delivery: uptake mechanism and transport pathways. Bioconjug. J. Achieving nanocarriers with low or no toxicity for the organism and the environment is one of the biggest challenges in designing drug delivery nanosystems. doi: 10.1016/b978-0-12-817778-5.00008-7, Kovačević, A. Preparation, characterization, and in vivo study of rhein solid lipid nanoparticles for oral delivery. Similarly, we could think that there are still years to come before SLN/NLC enter the pharmaceutical market. ACS Chem. 103, 167–176. Introduction. ICH Harmonized Tripartite Guideline. (2002). J. Compositions and methods for treating ornithine transcarbamylase deficiency. The chapter concludes with a summary of in vivo data on the improvement in oral bioavailability of poorly soluble drugs through the use of solid lipid nanoparticle dispersions and the application of such systems in parenteral drug delivery, with a special focus on pharmacokinetics and biodistribution. Eur. Despite the fact that fenestrations in the spleen may filter out particles larger than 200 nm, particle deformability can allow large particles to squeeze through them and remain in the bloodstream (Park et al., 2017). • Class IV (high risk), for nanosystems of size below 100 nm and made of non-biodegradable materials. The above mentioned is particularly relevant in SLN/NLC area, since even with the experience accumulated in these years, very few trends are predictable. Nanotoxicological classification system (NCS) suggested by Keck and Müller (2013). For this, the currently active clinical trials on lipid nanoparticles were reviewed, with a brief discussion on what achievements or milestones are still to be reached, as a way of understanding the reasons for the scarce number of solid lipid nanoparticles undergoing clinical trials. Drug-Like Properties. For this, response surface methodologies (RSM) are usually employed (although other statistical techniques may apply, see for example (Amasya et al., 2019)]. Charact. A Physicochem. During the formation of the PC, the incorporation of proteins of the complement system also known as opsonins occur. Biotechnol. One of the lipid nanoparticles used for colon-tar geted. Pharm. clinical trials; drug delivery; nanostructured lipid carriers; nanotoxicity; pharmacodynamics; pharmacokinetics; routes of administration; solid lipid nanoparticles. doi: 10.1517/17425247.2014.938634, Souto, E. B., Doktorovova, S., Campos, J. R., Martins-Lopes, P., and Silva, A. M. (2019). doi: 10.1016/j.ejps.2018.11.022, Souza, A. L. R. D., Andreani, T., De Oliveira, R. N., Kiill, C. P., Santos, F. K. D., Allegretti, S. M., et al. A proof that they are still in their initial stages of research can be seen in the publications reviewed here, a large percentage of which are technological (and not disease) focused research, and usually lacking of a rationale cost/benefit analysis, a characteristic of the initial stages of any research. Rev. Conjugation of SLN with RGD increased in vitro antitumor efficacy and in vivo cytotoxicity in comparison with non-targeted SLN (Zheng et al., 2019). Targeted delivery and apoptosis induction of trans-resveratrol-ferulic acid loaded chitosan coated folic acid conjugate solid lipid nanoparticles in colon cancer cells. Biol. Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other varied sciences. B., Müller, R. H., Saviæ, S. D., Vuleta, G. M., and Keck, C. M. (2014). Brain delivery of curcumin using solid lipid nanoparticles and nanostructured lipid carriers: preparation, optimization, and pharmacokinetic evaluation. Biosci. Combined, these characteristics lead to the accumulation, only based on the size (i.e., passive targeting), of NPs in the tumor vicinity, a phenomenon known as the Enhanced Permeability and Retention (EPR) effect. Oral delivery of pH-responsive alginate microbeads incorporating folic acid-grafted solid lipid nanoparticles exhibits enhanced targeting effect against colorectal cancer: a dual-targeted approach. Systematic approaches like the quality by design (QbD) concepts, strongly related to the pharmaceutical industry, are very useful to comprehensively study and characterize the design space of the formulation. An SLN. US20200181584A1. (2020). B Biointerfaces 165, 37-44. doi: 10.1016/j.colsurfb.2018.02.011 -, Abd-Rabou A. doi: 10.1002/chin.200502271, Cacicedo, M. L., Ruiz, M. C., Scioli-Montoto, S., Ruiz, M. E., Fernández, M. A., Torres-Sanchez, R. M., et al. The book "Nanocosmetics and nanomedicines: new approaches for skin care” contains a summary of the most important nanocarriers for skin delivery. Regardless the details of each synthesis method, they all share the common feature of an energy-providing step, under the form of ultrasonic waves [probe-type sonication (Haque et al., 2018; Pandya et al., 2018; Scioli Montoto et al., 2018) or ultrasonic bath (Rajpoot and Jain, 2018; Rosière et al., 2018; Chirio et al., 2019), high pressures (de Jesus et al., 2013; Küçüktürkmen and Bozkır, 2018; Wang et al., 2018), high speed homogenization (Nakhlband et al., 2018; Sathya et al., 2018; Youssef et al., 2018), or even microwaves (Shah et al., 2016a)]. Higher in vitro cytotoxicity and BBB permeability were found for A-SLN, attributable to receptor-mediated endocytic processes (Kadari et al., 2018). Control. Perez-Garcia, C. G., Tachikawa, K., Matsuda, D., and Chivukula, P. (2019). (2019). doi: 10.1016/0168-3659(94)90047-7, Scioli Montoto, S., Sbaraglini, M. L. L., Talevi, A., Couyoupetrou, M., Di Ianni, M., Pesce, G. O. O., et al. Rev. J. Biopharm. Ideally, the drug carrier should be rapidly removed from the body after the drug has been released. Therefore, pharmaceutical chemists will always have to deal with the PK/PD & toxicity balance, and the aqueous solubility will remain to be a critical factor in drug discovery. A comparison of the lung clearance kinetics of solid lipid nanoparticles and liposomes by following the3H-labelled structural lipids after pulmonary delivery in rats. 4, 807–818. Rep. 8, 13253. doi: 10.1038/s41598-018-31693-y. This review starts with a brief overview of the characteristics of solid lipid nanoparticles and discusses the relevancy of performing systematic . Sci. This makes it virtually impossible to review topics in a comprehensive manner, that is, covering everything published to date with respect to a given topic. Sci. Sci. Rev. J. Pharm. (2017). Pharm. 110, 76–84. doi: 10.1016/j.ejpb.2018.09.012, Kakkar, V., Muppu, S. K., Chopra, K., and Kaur, I. P. (2013). Improved brain delivery of pueraria flavones via intranasal administration of borneol-modified solid lipid nanoparticles. J. Chem. (1993). These kinds of treatment can be considered improvements over direct protein administration which face numerous problems like enzyme degradation or misfolding (Kowalski et al., 2019). The current treatment is a low protein diet and ammonia scavenging medication, with future insights on liver transplantation (Peng et al., 2020). Neurosci. Eur. Degradability and clearance of inorganic nanoparticles for biomedical applications. Res. (4) Finally, in the same way that NPs protect the drug from degradation by enzymes present in GI lumen, they can also prevent/reduce the degradation by metabolic enzymes, as in the lopinavir example mentioned in the previous section (Ravi et al., 2014). Colloidal. Cells Nanomed. Perhaps the only example is the positive relationship between the amount of lipid and the particle size, which is verified in almost all the cases and independently of the drug and preparation method: all the review articles that include the study of particle size as a function of the lipid amount found a direct relationship between them, at least in part of the studied range, if not in all. Found insideThis book presents the advances in the use of lipid-based and inorganic nanomaterials for medical imaging, diagnosis, theranostics, and drug delivery. 3, 737–747. 473, 270–279. (2011). (2015). Cancer Res. Chih-Hung L, et al. Biopharm 85(3 Pt A), 339–345. (2017). There is no doubt that nanoformulations are extremely valuable tools for drug delivery applications; the current challenge is how to optimize them to ensure that they are safe, effective and scalable, so that they can be manufactured at an industrial level and advance to clinical use. 50, 148–176. doi: 10.1111/cbdd.13007, Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., and Mello, C. C. (1998). Surface Modification of Resorcinarene-Based Self-Assembled Solid Lipid Nanoparticles for Drug Targeting. J. Pharm. These nanoparticles are manufactured from solid or mixture of solid and liquid lipids and stabilized by emulsifiers. Production, characterization and sterilization. The small absolute values of ζ are not enough to prevent the coalescence of the NPs, which need to be further stabilized by steric repulsion. Crit. Lancet Oncol. (2018). Last, but not least, the economic aspect must be mentioned. (2018). These apparently inconsistent results may be explained by the fact that surface charge is not the only toxicity determinant of a NPs, and that other covariables (such as the chemical composition of the NP) may also be considered. Acta Proteins Proteom. Accordingly, the interaction with different macromolecules, when they are in contact with biological fluids, will be favored. doi: 10.1002/adma.201805730, Yao, M., McClements, D. J., Zhao, F., Craig, R. W., and Xiao, H. (2017). Although the previously described classification system may seem an excessively reductionist approach to the matter of nanotoxicology, it is a valuable tool in the current state of research of pharmaceutical nanovehicles. Rev. Therefore, the preparation of these dispersions necessarily implies transferring energy to the system, in order to generate very small particles, with very high specific surface area (Troy, 2000). This coating prevents or delays the formation of the PC and, thus, NPs exhibit a prolonged half-life in the blood compartment (Pelaz et al., 2015). The contents of this book reflect the wide interest in the field of polymer colloids with chapters covering the preparation and properties of conducting particles, as well as composite particles and swellable particles. Cellular uptake by macrophages (phagocytic cells) is reserved for those particles larger than 0.5-10 μm (Zhao et al., 2011). (2020). doi: 10.1016/j.conb.2018.12.014, Azarnezhad, A., Samadian, H., Jaymand, M., Sobhani, M., and Ahmadi, A. As mentioned in previous sections, SLN and NLC proved to be particularly promising for the enhancement of drugs oral BA, by avoiding their degradation in the GI tract, improving their solubility and dissolution rate, increasing their contact with the epithelium and/or minimizing their efflux by P-gp and other drug transporters. LNPs as a drug delivery vehicle were first approved in 2018 for the siRNA drug, Onpattro. Release 316, 359–380. Toxicol. Ther. A study by Fang et al. Solid lipid nanoparticles as an efficient drug delivery system of olmesartan medoxomil for the treatment of hypertension. 548, 609–624. This chapter summarizes various aspects of SLNs such as components and production of SLNs, drug loading, drug release, stability, and application of SLNs in drug delivery. (2004). Mater. Biotechnol. (2007). Their major advantage is possibly the use of biocompatible, environmental-friendly constituents and preparation methods. It is not easy, however, predicting the effect that the NPs composition and preparation method will have on the ζ, particle size (PS) and entrapment efficiency (%EE). 8600 Rockville Pike According to that system, a nanocarrier is placed in one of four categories according to their size and biodegradability (Figure 5): Figure 5.

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