Nanopharmaceutical Advanced Delivery Systems. Группа авторов
to the carriers achieved by engineering the surface of the carriers with moieties that can attach to receptors expressed abundantly by the diseased cells [1]. Nanoscience has revolutionized the field of drug delivery, tissue engineering, biosensors, and nano-biotechnology [2, 3]. Nanomaterials are considered as particles having size less than 100 nm in any one dimension. Based on this criterion, the nanomaterials are classified as zero-dimensional (0D), one-dimensional (1D), two-dimensional (2-D), and three-dimensional (3D). Particles are considered as 0-D nanomaterials when all the dimensions are in the nanoscale range, i.e., less than 100 nm. Two out of three dimensions in 1-D nanomaterials are in the nanoscale range (one dimension is in the macroscale range). Nanotubes, nanofibers, and nanorods are examples of 1-D nanomaterials. The 2-D nanomaterials have only one dimension in the nanoscale range; examples include nanofilms and nanocoatings. Bundles of nanotubes or nanorods, multilayer of nanofilms in which all the dimensions are in the macroscale range, are considered as 3-D nanomaterials [4].
Polymers (natural or synthetic), lipids, or metals are used in the preparation of nanoparticulate carriers, which impart characteristic properties to these carriers. The composition and method of preparation of nanocarriers define the micromeritics, surface morphology, chemical properties, mechanical properties, magnetic properties, conductivity, and stability [1] Owing to their nanosize, these carriers can be transported via active or passive mechanisms across the biological barriers/tissues/cells and deliver drug at the target site [2, 3]. Endocytic absorption of nanocarriers is one such mechanism that results in improved bioavailability of drugs, especially the poorly soluble ones. Alongside drugs, nanocarriers are also being used for delivery of genetic material, viz. DNA or RNA [5].
2.2 Classification of Nanoparticulate Carriers
Broadly, the nanoparticulate carriers (Figure 2.1) can be categorized as lipid-based systems, micelles, thernostics, polymeric carriers, and self-emulsifying drug delivery systems (SEDDSs) (Table 2.1a). The lipid-based systems consist of concentric assemblies of one or more lipid bilayers, formed from amphiphilic building blocks in the presence of water. Liposomes, solid lipid nanoparticles (SLNs), nanolipid carriers (NLCs), etc. belong to this category. SEDDSs correspond to the emulsion-based lipidic systems prepared using surface active agents that self-emulsify in the gastrointestinal tract. Micelles, reverse micelles, etc. employ micellar solubilization of drug in the aqueous phase. Each of these categories has been briefly discussed in the following sections. The list and the classification, though exhaustive, are not limited. Various parameters need to be considered while choosing the carrier system for drug delivery, viz. the interactive forces between the nanocarriers and the biological environment, morphology of the target tissue, conductivity and mechanical properties, composition, size and surface characteristics, drug loading and drug retention capacity, and mechanism of release of drug from the carriers. Recently, due to non-responsiveness to the conventional treatment therapy, application of nanocarriers for the treatment of tuberculosis is also being proposed. Table 2.1b mentions various types of nanoparticulate carriers that are being studied for treatment of tuberculosis.
2.2.1 Lipid-Based Nanocarriers
Liposomes, solid lipid nanoparticles (SLNs), nanolipid carriers (NLCs), phytosomes, etc., are lipid-based nanocarriers. The functionality of lipid-based carrier systems is based on the type and arrangement of the constituent lipids [11, 12]. Both solid and liquid lipids can be used in the preparation of these carrier systems. Alec Bangham discovered liposomes in early 1960s and defined them as vesicular structures consisting of bilayers of phospholipids and hydrophilic aqueous compartment(s) arranged concentrically [13]. The fluidity of the bilayer depends on the degree of saturation of phospholipids used in the preparation of liposomes. Relatively rigid and stable bilayers are formed by saturated phospholipids with long acyl chains (e.g., dipalmitoylphosphatidylcholine) in comparison to those formed using unsaturated lipids like phosphatidylcholine from natural sources (egg or soybean phosphatidylcholine) [14].
Figure 2.1 Diagrammatic representation of various nanoparticulate carriers: (a) liposome; (b) gold nanoparticle (GNP); (c) dendrimers; (d) quantum dots; (e) solid lipid nanoparticle (SLN); (f) nanostructured lipid carriers (NLC); (g) nanoemulsion; (h) micelles; (i) polymeric nanoparticle (nanocapsules); (j) polymeric nanoparticle (nanospheres); (k) nanoscaffolds; and (l) inverse micelle.
Table 2.1a Classification of nanoparticulate carrier systems.
| Nanoparticulate carrier systems | ||||
|---|---|---|---|---|
| Lipid-based systems | Micellar systems | Thernostics | Polymer-based systems | Self-emulsifying drug delivery systems |
| LiposomesSolid lipid nanoparticlesNanolipid carriers pH-sensitive lipid carriersThermo-responsive lipid carriers | Micelles | Gold nanoparticlesIron oxide nanoparticlesQuantum dots | Polymeric nanoparticles | Self-emulsifying drug delivery systems (SEDDSs)Self-micro-emulsifying drug delivery systems (SMEDDSs) |
Table 2.1b Targeted treatment of tuberculosis using various nano-carrier-based drug delivery system.
| Nanoparticulate carriers | Mechanism of action | Effect | References |
|---|---|---|---|
| Chitosan-based nanoparticles (CNPs) | Cellular uptake and upregulate expression of CD-80/86/40/MHC-II molecule on RAW264.7 cells | ROS generation and oxidative stress may lead to DNA damage | [6] |
| Ag85B-ESAT6-PLGA nanoparticle | Internalized by the THP-1 human macrophages increase in the production of total serum IgG, IFNγ, and TNFα cytokine levels | Immunomodulation and protection against Mtb | [7] |
| Pep-H conjugated gold nanoparticles (Pep-H-AuNPs) | Antimycobacterial activity against in vitro active as well as dormant tubercle bacilli | Pep-H showed marked reduction in intracellular mycobacterial growth & modulate host immune system | [8] |
| SPIO-MtbsAb-nanoparticles | Endocytosis | Target mycobacterial antigen and diagnose extrapulmonary TB | [9] |
|
G5 |