was not promising in delivering DPL into the brain due to its hydrophilicity, several cholinergic side effects, hepatotoxicity, and first-pass metabolism [126].
Fatouh et al. (2019) achieved sustained drug release and improved corneal penetration of Natamycin using solid lipid nanoparticles (NAT-SLNs). The result confirms the desirability of using NAT-SLNs as an ophthalmic delivery system for sustained, antifungal activity and also as an alternative to conventional drops in the treatment of deep corneal fungal keratosis [127].
Khosa et al. (2018) proposed that NLC formulations seem to be preferable to SLNs due to their smaller particle size and higher drug loading capabilities [128]. Moreover, few experiments with NLC formulations for drug delivery through the BBB have been performed. Song et al. (2016) developed Arginine-glycineaspartic acid peptide (RGD)-modified temozolomide NLCs and found them to possess higher cytotoxicity and tumor inhibition compared to the parent drug solution [129].
Antiretroviral medications can also be integrated in an SLN to improve effectiveness, reduce side effects, and promote the movement of drugs in the brain by crossing the blood-brain barrier [130]. SLN scan raises the gradient of local concentration of drugs and enhances the transfer of drugs to the brain via endocytotic pathways. When incorporated with SLNs, the bioavailability of antiretroviral drugs is improved in the brain.
SLNs demonstrate improved drug release profiles, including continuous and controlled release of pharmaceutical agents. Doxorubicin with polysorbate 80 nanoparticles also depicted 40% cure in rats in glioblastomas transplanted intracranially [130, 131]. The nanoemulsions are used as vehicles to deliver the bioactives, which otherwise suffer from poor bioavailability and patient noncompliance [132]. Nanoemulsion-based vaccine delivery provides positive outcomes against HIV infection and shows good prognosis when the desired site of activity is oral or nasal mucosa.
Crystalline mesophases may also have a positive impact on drug development properties, such as kinetics of degradation and drug release, and comprehensive investigation of disordered materials (structure, dynamics, and thermodynamics) for the stability of the pharmaceutical ingredients [133, 134]. It has been shown that development of crystalline mesophases imparts high drug payload, provides thermodynamic solubility, and improves the absorption of poorly soluble drugs very effectively [135]. At the periods, mesophases could yield similar benefits like amorphous materials, i.e., improved apparent solubility and higher dissolution rates compared to crystalline forms, while reducing the risk of physical instability and solution precipitation compared to amorphous forms [136].
In the delivery of therapeutic agents to the CNS, lipid-based nanocarriers are considered a promising drug delivery method. Due to the natural potential of lipophilic materials to target the BBB, lipid-based nanocarriers are expected to be effective for CNS therapeutic drug delivery. Lipid nanoparticles are considered bio-acceptable and biodegradable, which makes those less toxic and more desirable for brain targeting. The application of lipid nanocarriers as targeted drug delivery systems is provided with several improvements, including enhanced storage stability, easy production without organic solvent, the potential of steam sterilization, lyophilization, and large-scale production [137–139].
1.7.2 Application in Therapeutic Nucleic Acid Delivery
Lipid nanoacrriers have been extensively used in gene therapy. Nucleic acid-based therapeutics include siRNA, miRNA, plasmid DNA, oligodeoxynucleotides, and non-viral vectors. These are highly sensible and degradable, which need a carrier system that can provide good loading capabilities and impart targeting to the cells. Lipid carrier systems are the appropriate carrier system to deliver the nucleic acid-based therapeutics in the treatment of disease at the molecular level. Therefore, researchers have attempted to encapsulate nucleic acid into lipid carriers and targeted them to the diseased site.
In a recent study carried out by Yu et al. (2019), it was demonstrated that paclitaxel and siRNA delivered by separate liposomes exhibit less advantages over the combination of paclitaxel and siRNA using AS1411 functional liposomes, which actively enhances the number of apoptotic cells and decreases angiogenesis [138].
There are several commercial products available in the market such as Lipofectine and Lipofect AMINE, which are the liposomal drug delivery system used for nucleic acid delivery through lipid nanocarriers [139].
Table 1.4 List of the drug as lipid nanocarriers under clinical investigation.
| Drug | Company | Disease | References |
| ND-L02-s0201 | Nitto Denko Corporation | Fibrosis | [140] |
| ALN-VSP02 | Alnylam Pharmaceuticals | Solid tumors | [141] |
| ALN-TTR02 | Amyloidosis | [142] | |
| ALN-PCS02 | Hypercholesterolemia | [143] | |
| DCR-MYC | Dicerna Pharmaceuticals | Multiple Myeloma | [144] |
| ARB-001467 | Arbutus Biopharma | Hepatitis B | [145] |
| TKM-100201 | Tekmira Pharmaceuticals | Ebola Virus Infection | [146] |
| siRNA-EphA2-DOPC | M.D. Anderson Cancer Center | Advanced cancers | [147] |
Similarly, few other examples of the nucleic acid delivery through lipid carriers that are under clinical investigation are given in Table 1.4.
1.7.3 Application in Delivery of Peptide/Hormone
Various lipid-based nanocarriers such as SLNs and liposomes have attempted to deliver peptide hormones such as Insulin, Gonadorelin, Levothyroxine, BSA, etc. In these categories, most of the lipid nanocarriers have demonstrated effectiveness in the delivery of hormones [148–150]. Various kinds of carriers explored to deliver peptides are given in Table 1.5.
1.8 Conclusion
Several nanocarriers have been explored for drug delivery application. However, majority of them do suffer from some known limitations such as low solubility of drugs, lack of targeting, toxicological profile, and physiochemical properties of individual carrier system. To overcome these issues, lipid-based carriers emerged to overcome these barriers and to ensure effective treatments for vulnerable patients in the past three decades. In nanotechnology platforms, lipid-based nanocarriers received notable attention in the field of drug delivery. Lipid nanoparticles such as SLNs, NLCs, SEDDS, crystalline mesophases, liposomes, and nanoemulsions are most widely used carriers in drug delivery due to their excellent pharmacokinetic/pharmacodynamics
